TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A.

A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord1. A major function of TDP-43 is as a repressor of cryptic exon inclusion during RNA splicing2-4. Single nucleotide polymorphisms in UNC13A are among the strongest hits associated with FTD and ALS in human genome-wide association studies5,6, but how those variants increase risk for disease is unknown. Here we show that TDP-43 represses a cryptic exon-splicing event in UNC13A. Loss of TDP-43 from the nucleus in human brain, neuronal cell lines and motor neurons derived from induced pluripotent stem cells resulted in the inclusion of a cryptic exon in UNC13A mRNA and reduced UNC13A protein expression. The top variants associated with FTD or ALS risk in humans are located in the intron harbouring the cryptic exon, and we show that they increase UNC13A cryptic exon splicing in the face of TDP-43 dysfunction. Together, our data provide a direct functional link between one of the strongest genetic risk factors for FTD and ALS (UNC13A genetic variants), and loss of TDP-43 function.

Stability and Cooling of the C_{7}

We have studied the stability of the smallest long-lived all carbon molecular dianion (C_{7}^{2-}) in new time domains and with a single ion at a time using a cryogenic electrostatic ion-beam storage ring. We observe spontaneous electron emission from internally excited dianions on millisecond timescales and monitor the survival of single colder C_{7}^{2-} molecules on much longer timescales. We find that their intrinsic lifetime exceeds several minutes-6 orders of magnitude longer than established from earlier experiments on C_{7}^{2-}. This is consistent with our calculations of vertical electron detachment energies predicting one inherently stable isomer and one isomer which is stable or effectively stable behind a large Coulomb barrier for C_{7}^{2-}→C_{7}^{-}+e^{-} separation.

Patient-reported outcome measures for physical function in cancer patients: content comparison of the EORTC CAT Core, EORTC QLQ-C30, SF-36, FACT-G, and PROMIS measures using the International Classification of Functioning, Disability and Health.

BACKGROUND: Patient-reported physical function (PF) is a key endpoint in cancer clinical trials. Using complex statistical methods, common metrics have been developed to compare scores from different patient-reported outcome (PRO) measures, but such methods do not account for possible differences in questionnaire content. Therefore, the aim of our study was a content comparison of frequently used PRO measures for PF in cancer patients. METHODS: Relying on the framework of the International Classification of Functioning, Disability and Health (ICF) we categorized the item content of the physical domains of the following measures: EORTC CAT Core, EORTC QLQ-C30, SF-36, PROMIS Cancer Item Bank for Physical Function, PROMIS Short Form for Physical Function 20a, and the FACT-G. Item content was linked to ICF categories by two independent reviewers. RESULTS: The 118 items investigated were assigned to 3 components ('d - Activities and Participation', 'b - Body Functions', and 'e - Environmental Factors') and 11 first-level ICF categories. All PF items of the EORTC measures but one were assigned to the first-level ICF categories 'd4 - Mobility' and 'd5 - Self-care', all within the component 'd - Activities and Participation'. The SF-36 additionally included item content related to 'd9 - Community, social and civic life' and the PROMIS Short Form for Physical Function 20a also included content related to 'd6 - domestic life'. The PROMIS Cancer Item Bank (v1.1) covered, in addition, two first-level categories within the component 'b - Body Functions'. The FACT-G Physical Well-being scale was found to be the most diverse scale with item content partly not covered by the ICF framework. DISCUSSION: Our results provide information about conceptual differences between common PRO measures for the assessment of PF in cancer patients. Our results complement quantitative information on psychometric characteristics of these measures and provide a better understanding of the possibilities of establishing common metrics.

Asc-Seurat: analytical single-cell Seurat-based web application.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of transcriptomes, arising as a powerful tool for discovering and characterizing cell types and their developmental trajectories. However, scRNA-seq analysis is complex, requiring a continuous, iterative process to refine the data and uncover relevant biological information. A diversity of tools has been developed to address the multiple aspects of scRNA-seq data analysis. However, an easy-to-use web application capable of conducting all critical steps of scRNA-seq data analysis is still lacking. We present Asc-Seurat, a feature-rich workbench, providing an user-friendly and easy-to-install web application encapsulating tools for an all-encompassing and fluid scRNA-seq data analysis. Asc-Seurat implements functions from the Seurat package for quality control, clustering, and genes differential expression. In addition, Asc-Seurat provides a pseudotime module containing dozens of models for the trajectory inference and a functional annotation module that allows recovering gene annotation and detecting gene ontology enriched terms. We showcase Asc-Seurat's capabilities by analyzing a peripheral blood mononuclear cell dataset. CONCLUSIONS: Asc-Seurat is a comprehensive workbench providing an accessible graphical interface for scRNA-seq analysis by biologists. Asc-Seurat significantly reduces the time and effort required to analyze and interpret the information in scRNA-seq datasets.

Model-based convolutional neural network approach to underwater source-range estimation.

This paper is part of a special issue on machine learning in acoustics. A model-based convolutional neural network (CNN) approach is presented to test the viability of this method as an alternative to conventional matched-field processing (MFP) for underwater source-range estimation. The networks are trained with simulated data generated under a particular model of the environment. When tested with data simulated in environments that deviate slightly from the training environment, this approach shows improved prediction accuracy and lower mean-absolute-error (MAE) compared to MFP. The performance of this model-based approach also transfers to real data, as demonstrated separately with field data collected in the Beaufort Sea and off the coast of Southern California. For the former, the CNN predictions are consistent with expected source range while for the latter, the CNN estimates have lower MAE compared to MFP. Examination of the trained CNNs' intermediate outputs suggests that the approach is more constrained than MFP from outputting very inaccurate predictions when there is a slight environmental mismatch. This improvement appears to be at the expense of decreased certainty in the correct source range prediction when the environment is precisely modeled.

The relationship between time to diagnose and diagnostic accuracy among internal medicine residents: a randomized experiment.

BACKGROUND: Diagnostic errors have been attributed to cognitive biases (reasoning shortcuts), which are thought to result from fast reasoning. Suggested solutions include slowing down the reasoning process. However, slower reasoning is not necessarily more accurate than faster reasoning. In this study, we studied the relationship between time to diagnose and diagnostic accuracy. METHODS: We conducted a multi-center within-subjects experiment where we prospectively induced availability bias (using Mamede et al.'s methodology) in 117 internal medicine residents. Subsequently, residents diagnosed cases that resembled those bias cases but had another correct diagnosis. We determined whether residents were correct, incorrect due to bias (i.e. they provided the diagnosis induced by availability bias) or due to other causes (i.e. they provided another incorrect diagnosis) and compared time to diagnose. RESULTS: We did not successfully induce bias: no significant effect of availability bias was found. Therefore, we compared correct diagnoses to all incorrect diagnoses. Residents reached correct diagnoses faster than incorrect diagnoses (115 s vs. 129 s, p < .001). Exploratory analyses of cases where bias was induced showed a trend of time to diagnose for bias diagnoses to be more similar to correct diagnoses (115 s vs 115 s, p = .971) than to other errors (115 s vs 136 s, p = .082). CONCLUSIONS: We showed that correct diagnoses were made faster than incorrect diagnoses, even within subjects. Errors due to availability bias may be different: exploratory analyses suggest a trend that biased cases were diagnosed faster than incorrect diagnoses. The hypothesis that fast reasoning leads to diagnostic errors should be revisited, but more research into the characteristics of cognitive biases is important because they may be different from other causes of diagnostic errors.

Transport Selectivity of Nuclear Pores, Phase Separation, and Membraneless Organelles.

Nuclear pore complexes (NPCs) provide a selective passageway for receptor-mediated active transport between nucleus and cytoplasm, while maintaining the distinct molecular compositions of both compartments at large. In this review we discuss how NPCs gain a remarkable sorting selectivity from non-globular FG domains and their phase separation into dense polymer meshworks. The resulting sieve-like FG hydrogels are effective barriers to normal macromolecules but are at the same time highly permeable to shuttling nuclear transport receptors, which bind to FG motifs as well as to their designated cargoes. Phase separation driven by disordered protein domains was recently also recognized as being pivotal to the formation of membraneless organelles, making it an important emerging principle in cell biology.

7X multiplexed, optofluidic detection of nucleic acids for antibiotic-resistance bacterial screening.

Rapid and accurate diagnosis of bacterial infections resistant to multiple antibiotics requires development of new bio-sensors for differentiated detection of multiple targets. This work demonstrates 7x multiplexed detection for antibiotic-resistance bacterial screening on an optofluidic platform. We utilize spectrally multiplexed multi-spot excitation for simultaneous detection of nucleic acid strands corresponding to bacterial targets and resistance genes. This is enabled by multi-mode interference (MMI) waveguides integrated in an optofluidic device. We employ a combinatorial three-color labeling scheme for the nucleic acid assays to scale up their multiplexing capability to seven different nucleic acids, representing three species and four resistance genes.

Spontaneous Electron Emission from Hot Silver Dimer Anions: Breakdown of the Born-Oppenheimer Approximation.

We report the first experimental evidence of spontaneous electron emission from a homonuclear dimer anion through direct measurements of Ag_{2}^{-}→Ag_{2}+e^{-} decays on milliseconds and seconds timescales. This observation is very surprising as there is no avoided crossing between adiabatic energy curves to mediate such a process. The process is weak, yet dominates the decay signal after 100 ms when ensembles of internally hot Ag_{2}^{-} ions are stored in the cryogenic ion-beam storage ring, DESIREE, for 10 s. The electron emission process is associated with an instantaneous, very large reduction of the vibrational energy of the dimer system. This represents a dramatic deviation from a Born-Oppenheimer description of dimer dynamics.

Temporal and spatial characteristics of the Beaufort Sea ambient noise environment.

Underwater ambient noise from the Beaufort Sea, collected in March 2016, is analyzed to investigate the effect that environmental changes in the region have on the spatial and temporal characteristics of the ice-generated ambient noise. In particular, the influx of warm Pacific water, so called the Beaufort Lens, has dramatically altered the level and vertical directionality of ambient noise, creating a low noise zone in the ∼75-250 m depth interval with a noise notch at low grazing angles. It is also demonstrated how the observed noise vertical directionality is consistent with ice-mechanical activity along an active pressure ridge ∼30-50 km from the recording array, as shown by satellite imagery. The discrete ranges to this ice activity explain the peak arrival angles between -10 to -15 degrees in noise vertical directionality, as well as the horizontal noise notch. Transient noise events associated with the ice activity are analyzed using an image processing approach with hierarchical clustering applied to the recorded spectrograms. The observed events are grouped into three categories-short-time-broadband, long-time-narrowband, and long-time-broadband-each likely generated through a different mechanism by the ice cover. The spectral and temporal distribution of these transients are discussed.

Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma.

BACKGROUND: Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established. PATIENTS AND METHODS: This academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N = 167) or nivolumab (N = 18) in the absence of disease progression (PD) or treatment limiting toxicity (TLT) at 14 medical centres across Europe and Australia. RESULTS: Median time on treatment was 12 months (range 0.7-43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18 months (range 0.7-48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12 months (range 2-23). PD was less frequent in patients with CR (14%) compared with patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new antitumour response. CONCLUSIONS: In this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared with clinical trials. In patients obtaining a CR, and being treated for >6 months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed antitumour activity in some patients. CLINICAL TRIAL REGISTRATION: NCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970?cond=melanoma&cntry=BE&city=Jette&rank=3).

Decay pathways for protonated and deprotonated adenine molecules.

We have measured fragment mass spectra and total destruction cross sections for protonated and deprotonated adenine following collisions with He at center-of-mass energies in the 20-240 eV range. Classical and ab initio molecular dynamics simulations are used to provide detailed information on the fragmentation pathways and suggest a range of alternative routes compared to those reported in earlier studies. These new pathways involve, for instance, losses of HNC molecules from protonated adenine and losses of NH2 or C3H2N2 from deprotonated adenine. The present results may be important to advance the understanding of how biomolecules may be formed and processed in various astrophysical environments.

Preemptive endoluminal vacuum therapy to reduce anastomotic leakage after esophagectomy: a game-changing approach?

Endoluminal vacuum therapy (EVT) is an accepted treatment for anastomotic leakage (AL) after esophagectomy. A novel concept is to use this technology in a preemptive setting, with the aim to reduce the AL rate and postoperative morbidity. Preemptive EVT (pEVT) was performed intraoperatively in 19 consecutive patients undergoing minimally invasive esophagectomy, immediately after completion of esophagogastrostomy. Twelve patients (63%) were high-risk cases with severe comorbidity. The EVT device was removed routinely three to six (median 5) days after esophagectomy. The endpoints of this study were AL rate and postoperative morbidity. There were 20 anastomoses at risk in 19 patients. One patient (5.3%) experienced major morbidity (Clavien-Dindo grade IIIb) unrelated to anastomotic healing. He underwent open reanastomosis at postoperative day 12 with pEVT for redundancy of the gastric tube and failure of transition to oral diet. Mortality after 30 days was 0% and anastomotic healing was uneventful in 19/20 anastomoses (95%). One minor contained AL healed after a second course of EVT. Except early proximal dislodgement in one patient, there were no adverse events attributable to pEVT. The median comprehensive complication index 30 days after surgery was 20.9 (IQR 0-26.2). PEVT appears to be a safe procedure that may have the potential to improve surgical outcome in patients undergoing esophagectomy.

Spectral, spatial, and temporal characteristics of underwater ambient noise in the Beaufort Sea in 1994 and 2016.

Climate induced changes in the Arctic Ocean have severely impacted underwater acoustic communication and navigation; understanding underwater noise characteristics is critical to improving the performance of these operations. Ambient noise from the Beaufort Sea recorded in experiments more than 20 years apart (SIMI94 and ICEX16) are compared to determine differences that may be attributed to the region's rapidly changing environment. Spectral comparison shows noise within 20-350 Hz is ∼30 dB louder in 1994 than 2016; however, this is likely due to higher array self noise during SIMI94. Beamforming results show ambient noise vertical directionality is focused near the horizontal during SIMI94 but more spread in elevation during ICEX16, with a robust noise notch at the horizontal. Numerical modeling demonstrates that this difference may be attributed to ambient noise during ICEX16 being dominated by surface noise sources at discrete ranges rather than the historical assumption of a continuous and uniform distribution of sources. Temporal statistics of transient ice events show more acoustic activity during SIMI94 than ICEX16 and appear to support the new proposed surface source distribution for ICEX16.

Does providing the correct diagnosis as feedback after self-explanation improve medical students diagnostic performance?

BACKGROUND: Self-explanation without feedback has been shown to improve medical students' diagnostic reasoning. While feedback is generally seen as beneficial for learning, available evidence of the value of its combination with self-explanation is conflicting. This study investigated the effect on medical students' diagnostic performance of adding immediate or delayed content-feedback to self-explanation while solving cases. METHODS: Ninety-four 3rd-year students from a Canadian medical school were randomly assigned to three experimental conditions (immediate-feedback, delayed-feedback, control). In the learning phase, all students solved four clinical cases by giving i) the most likely diagnosis, ii) two main arguments supporting this diagnosis, and iii) two plausible alternative diagnoses, while using self-explanation. The immediate-feedback group was given the correct diagnosis after each case; delayed-feedback group received the correct diagnoses only after the four cases; control group received no feedback. One week later, all students solved four near-transfer (i.e., same final diagnosis as the learning cases but different scenarios) and four far-transfer cases (i.e., different final diagnosis from the learning cases and different scenarios) by answering the same three questions. Students' diagnostic accuracy (score for the response to the first question only) and diagnostic performance (combined score of responses to the three questions) scores were assessed in each phase. Four one-way ANOVAs were performed on each of the two scores for near and far-transfer cases. RESULTS: There was a significant effect of experimental condition on diagnostic accuracy on near-transfer cases (p < .05). The immediate-feedback and delayed-feedback groups performed equally well, both better than control (respectively, mean = 90.73, standard deviation =10.69; mean = 89.92, standard deviation = 13.85; mean = 82.03, standard deviation = 17.66). The experimental conditions did not significantly differ on far-transfer cases. CONCLUSIONS: Providing feedback to students in the form of the correct diagnosis after using self-explanation with clinical cases is potentially beneficial to improve their diagnostic accuracy but this effect is limited to similar cases. Further studies should explore how more elaborated feedback combined with self-explanation may impact students' diagnostic performance on different cases.

Identifying and Integrating Parent Priorities for Psychosocial Support Services in a Pediatric Cystic Fibrosis Clinic.

Engaging parents early in the development of psychosocial support programs in cystic fibrosis (CF) clinics may enable services and care team recommendations to be tailored appropriately. This pilot study identified psychosocial priorities of parents of children with CF related to treatment adherence, parent/child mental health, and CF-related communication. Forty parents of children with CF (2 months to 17 years) completed an anonymous 17-item survey during routine clinic visits that assessed priorities related to psychosocial services. Elements of a quality improvement framework were used to develop the survey and determine recommendations based on findings. Parents reported the most interest in support related to improving adherence to respiratory therapies and helping children complete treatments independently. Other priority areas included services that helped children cope with feelings of isolation or abnormality due to CF and strategies to improve communication with the care team. Additionally, the majority of families indicated that they preferred receiving psychosocial services during routine clinic visits, followed by periodic parent workshops. Based on survey results, the psychosocial team at our center developed a survey/response model (e.g., roundtables, workshops) that may serve useful for other CF care teams as they identify the priorities of parents and adapt to their needs.

[Uveal Melanoma Cell Under Oxidative Stress - Influence of VEGF and VEGF-Inhibitors]. / Uveale Melanomzellen unter oxidativem Stress ­ Einfluss von VEGF und VEGF-Inhibitoren.

BACKGROUND: The role of oxidative stress in cancer is complex. While the pathological alterations induced by oxidative stress may be involved in the induction of tumours, in the late stages of tumour development, it can facilitate the loss of tumour cells and might even prevent metastasis. Tumour cells show metabolic alterations, often inducing an increased production of reactive oxygen species, which makes these cells particularly vulnerable to additional oxidative stress. This is an important mode of action in the use of many chemotherapeutics and in the application of ionizing radiation. Uveal melanoma is the most frequent primary tumour in the adult eye. For metastasis of this tumour, which affects about 50 % of the patients, no appropriate treatment is currently available. However, the primary tumour can efficiently be treated with ionizing radiation. A frequent side effect of this treatment is radiation retinopathy, which is treated with vascular endothelial growth factor (VEGF) antagonists. A therapy of the primary tumour with VEGF antagonists is under discussion. So far, little data is available on this subject, however, a paradoxical worsening of the situation has been found in a mouse model of uveal melanoma treated with bevacizumab. METHODS: We have investigated the effect of VEGF and of the VEGF-antagonist bevacizumab on the survival of five different melanoma cell lines under oxidative stress treatment with hydrogen peroxide. In addition, we investigated the expression of relevant proteins and the effect of bevacizumab on the proliferation of the cells as well as its effect on the angiogenic behaviour of endothelial cells, co-cultured with uveal melanoma cells. RESULTS: Our study showed that not only VEGF but also, paradoxically, the VEGF-antagonist bevacizumab is able to protect uveal melanoma cells from oxidative stress-induced cell death. Bevacizumab did not influence the proliferation of the cells and showed only limited effectiveness to reduce angiogenic structures. CONCLUSION: Considering that oxidative stress is the mode of action for ionizing radiation to induce cell death, a protective effect of bevacizumab on uveal melanoma cells against oxidative stress is worrisome and argues against the use of VEGF in uveal melanoma.

De-O-Acetylation of mucin-derived sialic acids by recombinant NanS-p esterases of Escherichia coli O157:H7 strain EDL933.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain EDL933 encodes the single chromosomal 9-O-acetylesterase NanS, and several copies of prophage-encoded 9-O-acetylesterases (NanS-p). These enzymes have recently been shown to cleave 5-N-acetyl-9-O-acetyl neuraminic acid (Neu5,9Ac2) to yield de-O-acetylated Neu5Ac, the latter of which may serve as a carbon and/or nitrogen source. In the current study, we investigated the NanS- and NanS-p-mediated digestion of synthetic O-acetylated neuraminic acids and bovine submaxillary glands mucin (BSM)-derived O-acetylneuraminic acids by high-performance thin-layer chromatography (HPTLC) and nano electrospray ionization mass spectrometry (nanoESI MS). Initial HPTLC analyses showed the expected activity of NanS and NanS-p variants for Neu5,9Ac2. However, all tested enzymes were unable to de-O-acetylate 5-N-acetyl-4-O-acetylneuraminic acid (Neu5,4 Ac2) in our test system. The nanoESI MS analysis of neuraminic acids after treatment of BSM with NanS-p gave evidence that NanS-p variants of EHEC O157:H7 strain EDL933 cleave off O-acetyl groups from mono-, di-, and tri-O-acetylated Neu5Ac and N-glycolylneuraminic acid (Neu5Gc), regardless of the carbon positions C7, C8 or C9 of the acetate esters. This enzyme activity leads to neuraminidase-accessible Neu5Ac and Neu5Gc on mucin glycans. Moreover, we could demonstrate by HPTLC analyses that recombinant Bacteroides thetaiotaomicron sialidase (BTSA-His) was able to cleave Neu5Ac and Neu5,9Ac2 from BSM and that the combination of BTSA-His with both NanS-His and NanS-p-His derivatives enhanced the release of de-O-acetylated core Neu5Ac and Neu5Gc from mammalian mucin O-glycans. Growth experiments with EHEC wildtype strain EDL933, its nanS and nanS/nanS-p1a-p7 mutant and exogenous BTSA-His in BSM demonstrated that the presence of BTSA-His enhanced growth of EDL933 and the nanS deletion mutant but not the nanS/nanS-p1a-p7 mutant. Thus, we hypothesize that the expression of sialic acid O-acetylesterases with a broad specificity could be an advantage in competition with the gut microbiota for nutrients and facilitate EHEC colonization in the human large intestine.

Homozygous XYLT2 variants as a cause of spondyloocular syndrome.

Spondyloocular syndrome (SOS) is a rare autosomal recessive, skeletal disorder. Two recent studies have shown that it is the result of biallelic sequence variants in the XYLT2 gene with pleiotropic effects in multiple organs, including retina, heart muscle, inner ear, cartilage, and bone. The XYLT2 gene encodes xylosyltransferase 2, which catalyzes the transfer of xylose (monosaccharide) to the core protein of proteoglycans (PGs) leading to initiating the process of PG assembly. SOS was originally characterized in 2 families A and B of Iraqi and Turkish origin, respectively. Using DNA from affected members of the same 2 families, we performed whole exome sequencing, which revealed 2 novel homozygous missense variants (c.1159C > T, p.Arg387Trp) and (c.2548G > C, p.Asp850His). Our findings extend the body of evidence that SOS is caused by homozygous variants in the XYLT2 gene. In addition, this report has extended the phenotypic description of SOS by adding follow-up data from 5 affected individuals in one of the two families, presented here.

Mutual Neutralization of O

We have measured total absolute cross sections for the mutual neutralization (MN) of O^{-} with O^{+} and N^{+}. A fine resolution (of about 50 meV) in the kinetic energy spectra of the product neutral atoms allows unique identification of the atomic states participating in the mutual neutralization process. Cross sections and branching ratios have also been calculated down to 1 meV center-of-mass collision energy for these two systems, with a multichannel Landau-Zener model and an asymptotic method for the ionic-covalent coupling matrix elements. The importance of two-electron processes in one-electron transfer is demonstrated by the dominant contribution of a core-excited configuration of the nitrogen atom in N^{+}+O^{-} collisions. This effect is partially accounted for by introducing configuration mixing in the evaluation of coupling matrix elements.