Search

Your search keyword '"Neale A"' showing total 49,257 results
Start Over Author "Neale A"
49,257 results on '"Neale A"'

1. Motor imagery drives the effects of combined action observation and motor imagery on corticospinal excitability for coordinative lower-limb actions

Author

Neza Grilc, Ashika Chembila Valappil, Neale A. Tillin, Omar S. Mian, David J. Wright, Paul S. Holmes, Federico Castelli, and Adam M. Bruton

Subjects
Medicine, Science
Abstract

Abstract Combined action observation and motor imagery (AOMI) facilitates corticospinal excitability (CSE) and may potentially induce plastic-like changes in the brain in a similar manner to physical practice. This study used transcranial magnetic stimulation (TMS) to explore changes in CSE for AOMI of coordinative lower-limb actions. Twenty-four healthy adults completed two baseline (BLH, BLNH) and three AOMI conditions, where they observed a knee extension while simultaneously imagining the same action (AOMICONG), plantarflexion (AOMICOOR-FUNC), or dorsiflexion (AOMICOOR-MOVE). Motor evoked potential (MEP) amplitudes were recorded as a marker of CSE for all conditions from two knee extensor, one dorsi flexor, and two plantar flexor muscles following TMS to the right leg representation of the left primary motor cortex. A main effect for experimental condition was reported for all three muscle groups. MEP amplitudes were significantly greater in the AOMICONG condition compared to the BLNH condition (p = .04) for the knee extensors, AOMICOOR-FUNC condition compared to the BLH condition (p = .03) for the plantar flexors, and AOMICOOR-MOVE condition compared to the two baseline conditions for the dorsi flexors (ps ≤ .01). The study findings support the notion that changes in CSE are driven by the imagined actions during coordinative AOMI.

Published
2024
Full Text
View/download PDF

2. Home-based resistance training performed at either fast or slow speeds improves power output in older adults

Author

Kosuke Hirata, Mari Ito, Yuta Nomura, Chiho Kawashima, Tsukasa Yoshida, Yosuke Yamada, Neale A. Tillin, Geoffrey A. Power, and Ryota Akagi

Subjects
Muscle architecture, Body mass-based training, Sit-to-stand, Isotonic contraction, Medicine, Biology (General), QH301-705.5
Abstract

Purpose: We investigated the effect of an unsupervised, body mass- home-based resistance training program in older adults performed at either a fast or slow contractile speed on changes to muscle-power, -volume, -architecture, and fatigue resistance of the knee extensors. Methods: Thirty-two male older adults (age 65–88 years) were separated into 1) fast-speed exercise (Fast-group), 2) slow-speed exercise (Slow-group), and 3) no exercise (Control-group) groups. Participants in the exercise groups performed 30–45 repetitions of knee-extension and sit-to-stand exercises 3 times a week for 8 weeks with different exercise speed between the groups. Before and after the intervention period, the following variables were measured: Isotonic power, isometric strength, twitch contractile properties, muscle-activity, -architecture, and -quality, neuromuscular fatigue resistance of the knee extensors, and thigh muscle volume. Results: Peak power was increased in both the Fast-group (+24 %, P

Published
2024
Full Text
View/download PDF

3. Voluntary torque production is unaffected by changes in local thermal sensation during normothermia and hyperthermia

Author

Ralph Joseph Frederick Hills Gordon, Neale Anthony Tillin, Ceri Elen Diss, and Christopher James Tyler

Subjects
maximum voluntary contraction, neural drive, perceived thermal strain, Physiology, QP1-981
Abstract

Abstract This study investigated altered local head and neck thermal sensation on maximal and rapid torque production during voluntary contractions. Nine participants completed four visits in two environmental conditions: at rectal temperatures ∼39.5°C in hot (HOT; ∼50°C, ∼39% relative humidity) and ∼37°C in thermoneutral (NEU; ∼22°C, ∼46% relative humidity) conditions. Local thermal sensation was manipulated by heating in thermoneutral conditions and cooling in hot conditions. Evoked twitches and octets were delivered at rest. Maximum voluntary torque (MVT), normalised surface electromyography (EMG) and voluntary activation (VA) were assessed during brief maximal isometric voluntary contractions of the knee extensors. Rate of torque development (RTD) and EMG were measured during rapid voluntary contractions. MVT (P = 0.463) and RTD (P = 0.061) were similar between environmental conditions despite reduced VA (−6%; P = 0.047) and EMG at MVT (−31%; P = 0.019). EMG in the rapid voluntary contractions was also lower in HOT versus NEU during the initial 100 ms (−24%; P = 0.035) and 150 ms (−26%; P = 0.035). Evoked twitch (+70%; P

Published
2023
Full Text
View/download PDF

4. A High-Throughput Photon Processing Technique for Range Extension of SPAD-Based LiDAR Receivers

Author

Sarrah M. Patanwala, Istvan Gyongy, Hanning Mai, Andreas Abmann, Neale A. W. Dutton, Bruce R. Rae, and Robert K. Henderson

Subjects
Light detection and ranging (LiDAR), macro-pixel, Monte Carlo simulation, single photon avalanche diode (SPAD), synthetic 3D data, time-of-flight (ToF), Electric apparatus and materials. Electric circuits. Electric networks, TK452-454.4
Abstract

There has recently been a keen interest in developing Light Detection and Ranging (LiDAR) systems using Single Photon Avalanche Diode (SPAD) sensors. This has led to a variety of implementations in pixel combining techniques and Time to Digital Converter (TDC) architectures for such sensors. This paper presents a comparison of these approaches and demonstrates a technique capable of extending the range of LiDAR systems with improved resilience to background conditions. A LiDAR system emulator using a reconfigurable SPAD array and FPGA interface is used to compare these different techniques. A Monte Carlo simulation model leveraging synthetic 3D data is presented to visualize the sensor performance on realistic automotive LiDAR scenes.

Published
2022
Full Text
View/download PDF

5. Training-Free Mitigation of Language Reasoning Degradation After Multimodal Instruction Tuning

Author

Ratzlaff, Neale, Luo, Man, Su, Xin, Lal, Vasudev, and Howard, Phillip

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Artificial Intelligence
Abstract

Multimodal models typically combine a powerful large language model (LLM) with a vision encoder and are then trained on multimodal data via instruction tuning. While this process adapts LLMs to multimodal settings, it remains unclear whether this adaptation compromises their original language reasoning capabilities. In this work, we explore the effects of multimodal instruction tuning on language reasoning performance. We focus on LLaVA, a leading multimodal framework that integrates LLMs such as Vicuna or Mistral with the CLIP vision encoder. We compare the performance of the original LLMs with their multimodal-adapted counterparts across eight language reasoning tasks. Our experiments yield several key insights. First, the impact of multimodal learning varies between Vicuna and Mistral: we observe a degradation in language reasoning for Mistral but improvements for Vicuna across most tasks. Second, while multimodal instruction learning consistently degrades performance on mathematical reasoning tasks (e.g., GSM8K), it enhances performance on commonsense reasoning tasks (e.g., CommonsenseQA). Finally, we demonstrate that a training-free model merging technique can effectively mitigate the language reasoning degradation observed in multimodal-adapted Mistral and even improve performance on visual tasks.

Published
2024

6. Debias your Large Multi-Modal Model at Test-Time with Non-Contrastive Visual Attribute Steering

Author

Ratzlaff, Neale, Olson, Matthew Lyle, Hinck, Musashi, Aflalo, Estelle, Tseng, Shao-Yen, Lal, Vasudev, and Howard, Phillip

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

Large Multi-Modal Models (LMMs) have demonstrated impressive capabilities as general-purpose chatbots that can engage in conversations about a provided input, such as an image. However, their responses are influenced by societal biases present in their training datasets, leading to undesirable differences in how the model responds when presented with images depicting people of different demographics. In this work, we propose a novel debiasing framework for LMMs that directly removes biased representations during text generation to decrease outputs related to protected attributes, or even representing them internally. Our proposed method is training-free; given a single image and a list of target attributes, we can ablate the corresponding representations with just one step of gradient descent on the image itself. Our experiments show that not only can we can minimize the propensity of LMMs to generate text related to protected attributes, but we can improve sentiment and even simply use synthetic data to inform the ablation while retaining language modeling capabilities on real data such as COCO or FACET. Furthermore, we find the resulting generations from a debiased LMM exhibit similar accuracy as a baseline biased model, showing that debiasing effects can be achieved without sacrificing model performance., Comment: 10 pages, 3 Figures, 3 Tables. arXiv admin note: text overlap with arXiv:2410.13976

Published
2024

7. Assessing methods for telluric removal on atmospheric retrievals of high-resolution optical exoplanetary transmission spectra

Author

Maguire, Cathal, Sedaghati, Elyar, Gibson, Neale P., Smette, Alain, and Pino, Lorenzo

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Recent advancements in ultra-stable ground-based high-resolution spectrographs have propelled ground-based astronomy to the forefront of exoplanet detection and characterisation. Retrieving accurate atmospheric parameters depends on accurate modelling and removal of the telluric contamination while preserving the faint underlying exoplanet signal. There exist many methods to model telluric contamination, whether directly modelling the Earth's transmission spectrum via radiative transfer modelling, or using a principal component analysis (PCA)-like reconstruction to fit the time-invariant features of a spectrum. We aimed to assess the efficacy of these various telluric removal methods in preserving the underlying exoplanetary spectra. We compared two of the most common telluric modelling and removal methods, molecfit and the PCA-like algorithm SysRem, using planetary transmission spectra injected into three high-resolution optical observations taken with ESPRESSO. These planetary signals were injected at orbital periods of P = 2 days and 12 days, resulting in differing changes in radial velocity during transit. We then retrieved various injected atmospheric model parameters in order to determine the efficacy of the telluric removal methods. For the close-in, high velocity injected signal, we found that SysRem performed better for species that are also present in the Earth's atmosphere across each of the datasets. As we moved to slower moving signals at larger orbital separations, for one of the three datasets, SysRem dampened the planetary H$_2$O signal. In contrast, the H$_2$O signal was preserved for the telluric modelling method, molecfit. However, this behaviour was not ubiquitous across all three of the injected datasets, with another dataset showing a more precise H$_2$O/Fe ratio when preprocessed with SysRem., Comment: 25 pages, 23 figures, appendices included. Accepted for publication in A&A

Published
2024

8. Debiasing Large Vision-Language Models by Ablating Protected Attribute Representations

Author

Ratzlaff, Neale, Olson, Matthew Lyle, Hinck, Musashi, Tseng, Shao-Yen, Lal, Vasudev, and Howard, Phillip

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Computation and Language, Computer Science - Machine Learning
Abstract

Large Vision Language Models (LVLMs) such as LLaVA have demonstrated impressive capabilities as general-purpose chatbots that can engage in conversations about a provided input image. However, their responses are influenced by societal biases present in their training datasets, leading to undesirable differences in how the model responds when presented with images depicting people of different demographics. In this work, we propose a novel debiasing framework for LVLMs by directly ablating biased attributes during text generation to avoid generating text related to protected attributes, or even representing them internally. Our method requires no training and a relatively small amount of representative biased outputs (~1000 samples). Our experiments show that not only can we can minimize the propensity of LVLMs to generate text related to protected attributes, but we can even use synthetic data to inform the ablation while retaining captioning performance on real data such as COCO. Furthermore, we find the resulting generations from a debiased LVLM exhibit similar accuracy as a baseline biased model, showing that debiasing effects can be achieved without sacrificing model performance., Comment: NeurIPS workshop on SafeGenAI, 10 pages, 2 figures

Published
2024

9. Hot Rocks Survey I : A shallow eclipse for LHS 1478 b

Author

August, Prune C., Buchhave, Lars A., Diamond-Lowe, Hannah, Mendonça, João M., Gressier, Amélie, Rathcke, Alexander D., Allen, Natalie H., Fortune, Mark, Jones, Kathryn D., Meier-Valdés, Erik A., Demory, Brice-Olivier, Espinoza, Nestor, Fisher, Chloe E., Gibson, Neale P., Heng, Kevin, Hoeijmakers, Jens, Hooton, Matthew J., Kitzmann, Daniel, and Prinoth, Bibiana

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

M dwarf systems offer a unique opportunity to study terrestrial exoplanetary atmospheres due to their smaller size and cooler temperatures. However, due to the extreme conditions these host stars impose, it is unclear whether their small, close-in rocky planets are able to retain any atmosphere at all. The Hot Rocks Survey aims to answer this question by targeting nine different M dwarf rocky planets spanning a range of planetary and stellar properties. LHS 1478 b orbits an M3-type star, has an equilibrium temperature of Teq = 585 K and experiences an instellation 21 times greater than that of Earth. We observe two secondary eclipses using photometric imaging at 15 um using the Mid-Infrared Instrument on the James Webb Space Telescope (JWST MIRI) to measure thermal emission from the dayside of the planet. We then compare these values to different atmospheric scenarios to evaluate potential heat transport and CO2 absorption signatures. We find a secondary eclipse depth of 146 +/- 56 ppm based on the first observation, while the second observation results in a non-detection due to significantly larger unexplained systematics. Based on the first observation alone, we can reject the null hypothesis of the dark (zero Bond albedo) no atmosphere bare rock model with a confidence level of 3.4 sigma. For an airless body with a Bond albedo of A=0.2, the significance decreases to 2.9 sigma. The secondary eclipse depth is consistent with the majority of atmospheric scenarios we considered, which all involve atmospheres which include different concentrations of CO2, and surface pressures from 0.1 to 10 bar. However, we stress that the two observations from our program do not yield consistent results, and more observations are needed to verify our findings. The Hot Rocks Survey serves as a relevant primer for future endeavors such as the Director's Discretionary Time (DDT) Rocky Worlds program., Comment: Submitted to A&A

Published
2024

10. Searching for Neutral Hydrogen Escape from the 120 Myr Old Sub-Neptune HIP94235b using HST

Author

Morrissey, Ava, Zhou, George, Huang, Chelsea X., Wright, Duncan, Auger, Caitlin, Rockcliffe, Keighley E., Newton, Elisabeth R., Rogers, James G., Gibson, Neale, Lowson, Nataliea, Mayorga, Laura C., and Wittenmyer, Robert A.

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

HIP94235 b, a 120 Myr old sub-Neptune, provides us the unique opportunity to study mass loss at a pivotal stage of the system's evolution: the end of a 100 million year (Myr) old phase of intense XUV irradiation. We present two observations of HIP94235 b using the Hubble Space Telescope's Space Telescope Imaging Spectrograph (HST/STIS) in the Ly-alpha wavelength region. We do not observe discernible differences across either the blue and red wings of the Ly-alpha line profile in and out of transit, and report no significant detection of outflowing neutral hydrogen around the planet. We constrain the rate of neutral hydrogen escaping HIP94235 b to an upper limit of 10^13 g/s, which remains consistent with energy-limited model predictions of 10^11 g/s. The Ly-alpha non-detection is likely due to the extremely short photoionization timescale of the neutral hydrogen escaping the planet's atmosphere. This timescale, approximately 15 minutes, is significantly shorter than that of any other planets with STIS observations. Through energy-limited mass loss models, we anticipate that HIP94235 b will transition into a super-Earth within a timescale of 1 Gyr., Comment: Accepted for publication in AJ

Published
2024

11. High-resolution atmospheric retrievals of WASP-76b transmission spectroscopy with ESPRESSO: Monitoring limb asymmetries across multiple transits

Author

Maguire, Cathal, Gibson, Neale P., Nugroho, Stevanus K., Fortune, Mark, Ramkumar, Swaetha, Gandhi, Siddharth, and de Mooij, Ernst

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

Direct atmospheric retrievals of exoplanets at high-resolution have recently allowed for a more detailed characterisation of their chemistry and dynamics from the ground. By monitoring the longitudinal distribution of species, as well as the varying vertical temperature structure and dynamics between the limbs of WASP-76b, across multiple transits, we aim to enhance our understanding of the 3D nature and chemical/dynamical evolution of such objects over the timescales of months/years. We present retrievals of three VLT/ESPRESSO observations of the ultra-hot Jupiter WASP-76b, including one not yet reported in the literature, from which we constrain the atmospheric abundances, vertical temperature structure, and atmospheric dynamics for both the leading and trailing limbs of the atmosphere separately, via novel rotational broadening kernels. We confirm the presence of VO recently reported in the atmosphere of WASP-76b. We find a uniform longitudinal distribution of Fe and Mg across the limbs of the atmosphere, for each of our transits, consistent with previous works as well as with stellar values. We constrain substellar Na/Fe and Cr/Fe ratios across each of our transits, consistent with previous studies of WASP-76b. Where constrained, V/Fe and VO/Fe ratios were also found to be broadly consistent between the limbs of the atmosphere for each of the transits, as well as with previous studies. However, for two of the transits, both V and VO were unconstrained in the leading limb, suggesting possible depletion due to recombination and condensation. The consistency of our constraints across multiple high-resolution observations, as well as with previous studies using varying modelling/retrieval frameworks and/or instruments, affirms the efficacy of high-resolution ground-based retrievals of exoplanetary atmospheres., Comment: Accepted for publication in Astronomy & Astrophysics. 23 pages, 16 figures (including appendix)

Published
2024
Full Text
View/download PDF

14. How do wavelength correlations affect transmission spectra? Application of a new fast and flexible 2D Gaussian process framework to transiting exoplanet spectroscopy

Author

Fortune, Mark, Gibson, Neale P., Foreman-Mackey, Daniel, Evans-Soma, Thomas M., Maguire, Cathal, and Ramkumar, Swaetha

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The use of Gaussian processes (GPs) is a common approach to account for correlated noise in exoplanet time series, particularly for transmission and emission spectroscopy. This analysis has typically been performed for each wavelength channel separately, with the retrieved uncertainties in the transmission spectrum assumed to be independent. However, the presence of noise correlated in wavelength could cause these uncertainties to be correlated, which could significantly affect the results of atmospheric retrievals. We present a method that uses a GP to model noise correlated in both wavelength and time simultaneously for the full spectroscopic dataset while avoiding the use of a 'common-mode' correction. To make this analysis computationally tractable, we introduce a new fast and flexible GP method that can analyse 2D datasets when the input points lie on a (potentially non-uniform) 2D grid - in our case a time by wavelength grid - and the kernel function has a Kronecker product structure. This simultaneously fits all light curves and enables the retrieval of the covariance matrix of the transmission spectrum. By testing on synthetic datasets, we demonstrate that our new approach can reliably recover atmospheric features contaminated by noise correlated in time and wavelength. In contrast, fitting each spectroscopic light curve separately performed poorly when wavelength-correlated noise was present. It frequently underestimated the uncertainty of the scattering slope and overestimated the uncertainty in the strength of sharp absorption peaks in transmission spectra. Two archival VLT/FORS2 transit observations of WASP-31b were re-analysed, with our method strongly constraining the presence of wavelength-correlated noise in both datasets and recovering significantly different constraints on atmospheric features such as the scattering slope and strength of sodium and potassium features., Comment: Language revised version accepted for publication in Astronomy & Astrophysics. 35 pages, 18 figures (including appendix)

Published
2024
Full Text
View/download PDF

15. Nightside clouds and disequilibrium chemistry on the hot Jupiter WASP-43b

Author

Bell, Taylor J., Crouzet, Nicolas, Cubillos, Patricio E., Kreidberg, Laura, Piette, Anjali A. A., Roman, Michael T., Barstow, Joanna K., Blecic, Jasmina, Carone, Ludmila, Coulombe, Louis-Philippe, Ducrot, Elsa, Hammond, Mark, Mendonça, João M., Moses, Julianne I., Parmentier, Vivien, Stevenson, Kevin B., Teinturier, Lucas, Zhang, Michael, Batalha, Natalie M., Bean, Jacob L., Benneke, Björn, Charnay, Benjamin, Chubb, Katy L., Demory, Brice-Olivier, Gao, Peter, Lee, Elspeth K. H., López-Morales, Mercedes, Morello, Giuseppe, Rauscher, Emily, Sing, David K., Tan, Xianyu, Venot, Olivia, Wakeford, Hannah R., Aggarwal, Keshav, Ahrer, Eva-Maria, Alam, Munazza K., Baeyens, Robin, Barrado, David, Caceres, Claudio, Carter, Aarynn L., Casewell, Sarah L., Challener, Ryan C., Crossfield, Ian J. M., Decin, Leen, Désert, Jean-Michel, Dobbs-Dixon, Ian, Dyrek, Achrène, Espinoza, Néstor, Feinstein, Adina D., Gibson, Neale P., Harrington, Joseph, Helling, Christiane, Hu, Renyu, Iro, Nicolas, Kempton, Eliza M. -R., Kendrew, Sarah, Komacek, Thaddeus D., Krick, Jessica, Lagage, Pierre-Olivier, Leconte, Jérémy, Lendl, Monika, Lewis, Neil T., Lothringer, Joshua D., Malsky, Isaac, Mancini, Luigi, Mansfield, Megan, Mayne, Nathan J., Mikal-Evans, Thomas, Molaverdikhani, Karan, Nikolov, Nikolay K., Nixon, Matthew C., Palle, Enric, de la Roche, Dominique J. M. Petit dit, Piaulet, Caroline, Powell, Diana, Rackham, Benjamin V., Schneider, Aaron D., Steinrueck, Maria E., Taylor, Jake, Welbanks, Luis, Yurchenko, Sergei N., Zhang, Xi, and Zieba, Sebastian

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5-12 $\mu$m with JWST's Mid-Infrared Instrument (MIRI). The spectra reveal a large day-night temperature contrast (with average brightness temperatures of 1524$\pm$35 and 863$\pm$23 Kelvin, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase curve shape and emission spectra strongly suggest the presence of nightside clouds which become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2$\sigma$ upper limit of 1-6 parts per million, depending on model assumptions)., Comment: 61 pages, 13 figures, 4 tables. This preprint has been submitted to and accepted in principle for publication in Nature Astronomy without significant changes

Published
2024

16. Association of leukemic molecular profile with efficacy of inotuzumab ozogamicin in adults with relapsed/refractory ALL.

Author

Zhao, Yaqi, Laird, A, Roberts, Kathryn, Yafawi, Rolla, Kantarjian, Hagop, DeAngelo, Daniel, Stelljes, Matthias, Liedtke, Michaela, Stock, Wendy, Gökbuget, Nicola, OBrien, Susan, Jabbour, Elias, Cassaday, Ryan, Loyd, Melanie, Olsen, Scott, Neale, Geoffrey, Liu, Xueli, Vandendries, Erik, Advani, Anjali, and Mullighan, Charles

Subjects
Humans, Inotuzumab Ozogamicin, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Adult, Female, Male, Middle Aged, Treatment Outcome, Aged, Recurrence, Antineoplastic Agents, Immunological, Young Adult, Drug Resistance, Neoplasm, Adolescent
Abstract

The phase 3 INO-VATE trial demonstrated higher rates of remission, measurable residual disease negativity, and improved overall survival for patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) who received inotuzumab ozogamicin (InO) vs standard-of-care chemotherapy (SC). Here, we examined associations between genomic alterations and the efficacy of InO. Of 326 randomized patients, 91 (InO, n = 43; SC, n = 48) had samples evaluable for genomic analysis. The spectrum of gene fusions and other genomic alterations observed was comparable with prior studies of adult ALL. Responses to InO were observed in all leukemic subtypes, genomic alterations, and risk groups. Significantly higher rates of complete remission (CR)/CR with incomplete count recovery were observed with InO vs SC in patients with BCR::ABL1-like ALL (85.7% [6/7] vs 0% [0/5]; P = .0076), with TP53 alterations (100% [5/5] vs 12.5% [1/8]; P = .0047), and in the high-risk BCR::ABL1- (BCR::ABL1-like, low-hypodiploid, KMT2A-rearranged) group (83.3% [10/12] vs 10.5% [2/19]; P < .0001). This retrospective, exploratory analysis of the INO-VATE trial demonstrated potential for benefit with InO for patients with R/R ALL across leukemic subtypes, including BCR::ABL1-like ALL, and for those bearing diverse genomic alterations. Further confirmation of the efficacy of InO in patients with R/R ALL exhibiting the BCR::ABL1-like subtype or harboring TP53 alterations is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT01564784.

Published
2024

17. A genome sequence for the threatened whitebark pine.

Author

Neale, David, Zimin, Aleksey, Meltzer, Amy, Bhattarai, Akriti, Amee, Maurice, Figueroa Corona, Laura, Puiu, Daniela, Wright, Jessica, De La Torre, Amanda, McGuire, Patrick, Timp, Winston, Salzberg, Steven, Wegrzyn, Jill, and Allen, Brian

Subjects
Pinus albicaulis, annotation, conifer, genome assembly, gymnosperm, whitebark pine, Pinus, Molecular Sequence Annotation, Genome, Plant, Genomics, Endangered Species, High-Throughput Nucleotide Sequencing
Abstract

Whitebark pine (WBP, Pinus albicaulis) is a white pine of subalpine regions in the Western contiguous United States and Canada. WBP has become critically threatened throughout a significant part of its natural range due to mortality from the introduced fungal pathogen white pine blister rust (WPBR, Cronartium ribicola) and additional threats from mountain pine beetle (Dendroctonus ponderosae), wildfire, and maladaptation due to changing climate. Vast acreages of WBP have suffered nearly complete mortality. Genomic technologies can contribute to a faster, more cost-effective approach to the traditional practices of identifying disease-resistant, climate-adapted seed sources for restoration. With deep-coverage Illumina short reads of haploid megagametophyte tissue and Oxford Nanopore long reads of diploid needle tissue, followed by a hybrid, multistep assembly approach, we produced a final assembly containing 27.6 Gb of sequence in 92,740 contigs (N50 537,007 bp) and 34,716 scaffolds (N50 2.0 Gb). Approximately 87.2% (24.0 Gb) of total sequence was placed on the 12 WBP chromosomes. Annotation yielded 25,362 protein-coding genes, and over 77% of the genome was characterized as repeats. WBP has demonstrated the greatest variation in resistance to WPBR among the North American white pines. Candidate genes for quantitative resistance include disease resistance genes known as nucleotide-binding leucine-rich repeat receptors (NLRs). A combination of protein domain alignments and direct genome scanning was employed to fully describe the 3 subclasses of NLRs. Our high-quality reference sequence and annotation provide a marked improvement in NLR identification compared to previous assessments that leveraged de novo-assembled transcriptomes.

Published
2024

18. Importance of Demand Side Unsteadiness on Opportunity for Space Heating Energy Saving

Author

Williams, Andrew Morgan, Brammer, John, Innerdale, Daniel, Ashcroft, Michael, Caldwell, Scott, Kiddell, David, Sadique, Monower, Amoaki-Attah, Joseph, Davies, Neale, di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Cui, Zhen-Dong, Series Editor, Lu, Xinzheng, Series Editor, and Berardi, Umberto, editor

Published
2025
Full Text
View/download PDF

19. The Role of the IGF-1 Signaling Cascade in Muscle Protein Synthesis and Anabolic Resistance in Aging Skeletal Muscle

Author

Richie D. Barclay, Nicholas A. Burd, Christopher Tyler, Neale A. Tillin, and Richard W. Mackenzie

Subjects
IP6K1, sarcopenia, aging, protein, resistance exercise, anabolic resistance, Nutrition. Foods and food supply, TX341-641
Abstract

Sarcopenia is defined as the combined loss of skeletal muscle strength, function, and/or mass with aging. This degenerative loss of muscle mass is associated with poor quality of life and early mortality humans. The loss of muscle mass occurs due to acute changes in daily muscle net protein balance (NPB). It is generally believed a poor NPB occurs due to reduced muscle protein synthetic responses to exercise, dietary amino acid availability, or an insensitivity of insulin to suppress breakdown. Hence, aging muscles appear to be resistant to the anabolic action of exercise and protein (amino acids or hormonal) when compared to their younger counterparts. The mechanisms that underpin anabolic resistance to anabolic stimuli (protein and resistance exercise) are multifactorial and may be partly driven by poor lifestyle choices (increased sedentary time and reduced dietary protein intake) as well as an inherent dysregulated mechanism in old muscles irrespective of the environmental stimuli. The insulin like growth factor 1 (IGF-1), Akt /Protein Kinase B and mechanistic target of rapamycin (mTOR) pathway is the primary driver between mechanical contraction and protein synthesis and may be a site of dysregulation between old and younger people. Therefore, our review aims to describe and summarize the differences seen in older muscle in this pathway in response to resistance exercise (RE) and describe approaches that researchers have sought out to maximize the response in muscle. Furthermore, this review will present the hypothesis that inositol hexakisphosphate kinase 1 (IP6K1) may be implicated in IGF-1 signaling and thus sarcopenia, based on recent evidence that IGF-1 and insulin share some intracellular bound signaling events and that IP6K1 has been implicated in skeletal muscle insulin resistance.

Published
2019
Full Text
View/download PDF

20. Fine-mapping across diverse ancestries drives the discovery of putative causal variants underlying human complex traits and diseases

Author

Yuan, Kai, Longchamps, Ryan J., Pardiñas, Antonio F., Yu, Mingrui, Chen, Tzu-Ting, Lin, Shu-Chin, Chen, Yu, Lam, Max, Liu, Ruize, Xia, Yan, Guo, Zhenglin, Shi, Wenzhao, Shen, Chengguo, Daly, Mark J., Neale, Benjamin M., Feng, Yen-Chen A., Lin, Yen-Feng, Chen, Chia-Yen, O’Donovan, Michael C., Ge, Tian, and Huang, Hailiang

Published
2024
Full Text
View/download PDF

22. Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation

Author

Carey, Caitlin E., Shafee, Rebecca, Wedow, Robbee, Elliott, Amanda, Palmer, Duncan S., Compitello, John, Kanai, Masahiro, Abbott, Liam, Schultz, Patrick, Karczewski, Konrad J., Bryant, Samuel C., Cusick, Caroline M., Churchhouse, Claire, Howrigan, Daniel P., King, Daniel, Davey Smith, George, Neale, Benjamin M., Walters, Raymond K., and Robinson, Elise B.

Published
2024
Full Text
View/download PDF

25. Investigation of a Human Case of Francisella tularensis Infection, United Kingdom, 2023

Author

Thompson, Ameeka, Brooks, Tim, Houlihan, Catherine, Rampling, Tommy, Umpleby, Helen, Hansford, Kayleigh, Medlock, Jolyon, Vaux, Alexander, Logan, Julie, Frost, Andrew, Neale, Sue, Wyllie, Stephen, Dodgson, Kirsty, Haigh, Dominic, Halim, Isra, Huq, Raqib, Riste, Michael, and Gordon, N. Claire

Subjects
Francisella tularensis -- Physiological aspects -- Case studies, Medical research, Medicine, Experimental, Tularemia -- Physiological aspects -- Case studies -- Causes of, Health
Abstract

Tularemia is a zoonotic disease caused by Franciscella tularensis, currently considered absent from the United Kingdom. We report a human case of F. tularensis subspecies holarctica infection diagnosed in the [...]

Published
2024
Full Text
View/download PDF

26. Gemini: A Family of Highly Capable Multimodal Models

Author

Gemini Team, Anil, Rohan, Borgeaud, Sebastian, Alayrac, Jean-Baptiste, Yu, Jiahui, Soricut, Radu, Schalkwyk, Johan, Dai, Andrew M., Hauth, Anja, Millican, Katie, Silver, David, Johnson, Melvin, Antonoglou, Ioannis, Schrittwieser, Julian, Glaese, Amelia, Chen, Jilin, Pitler, Emily, Lillicrap, Timothy, Lazaridou, Angeliki, Firat, Orhan, Molloy, James, Isard, Michael, Barham, Paul R., Hennigan, Tom, Lee, Benjamin, Viola, Fabio, Reynolds, Malcolm, Xu, Yuanzhong, Doherty, Ryan, Collins, Eli, Meyer, Clemens, Rutherford, Eliza, Moreira, Erica, Ayoub, Kareem, Goel, Megha, Krawczyk, Jack, Du, Cosmo, Chi, Ed, Cheng, Heng-Tze, Ni, Eric, Shah, Purvi, Kane, Patrick, Chan, Betty, Faruqui, Manaal, Severyn, Aliaksei, Lin, Hanzhao, Li, YaGuang, Cheng, Yong, Ittycheriah, Abe, Mahdieh, Mahdis, Chen, Mia, Sun, Pei, Tran, Dustin, Bagri, Sumit, Lakshminarayanan, Balaji, Liu, Jeremiah, Orban, Andras, Güra, Fabian, Zhou, Hao, Song, Xinying, Boffy, Aurelien, Ganapathy, Harish, Zheng, Steven, Choe, HyunJeong, Weisz, Ágoston, Zhu, Tao, Lu, Yifeng, Gopal, Siddharth, Kahn, Jarrod, Kula, Maciej, Pitman, Jeff, Shah, Rushin, Taropa, Emanuel, Merey, Majd Al, Baeuml, Martin, Chen, Zhifeng, Shafey, Laurent El, Zhang, Yujing, Sercinoglu, Olcan, Tucker, George, Piqueras, Enrique, Krikun, Maxim, Barr, Iain, Savinov, Nikolay, Danihelka, Ivo, Roelofs, Becca, White, Anaïs, Andreassen, Anders, von Glehn, Tamara, Yagati, Lakshman, Kazemi, Mehran, Gonzalez, Lucas, Khalman, Misha, Sygnowski, Jakub, Frechette, Alexandre, Smith, Charlotte, Culp, Laura, Proleev, Lev, Luan, Yi, Chen, Xi, Lottes, James, Schucher, Nathan, Lebron, Federico, Rrustemi, Alban, Clay, Natalie, Crone, Phil, Kocisky, Tomas, Zhao, Jeffrey, Perz, Bartek, Yu, Dian, Howard, Heidi, Bloniarz, Adam, Rae, Jack W., Lu, Han, Sifre, Laurent, Maggioni, Marcello, Alcober, Fred, Garrette, Dan, Barnes, Megan, Thakoor, Shantanu, Austin, Jacob, Barth-Maron, Gabriel, Wong, William, Joshi, Rishabh, Chaabouni, Rahma, Fatiha, Deeni, Ahuja, Arun, Tomar, Gaurav Singh, Senter, Evan, Chadwick, Martin, Kornakov, Ilya, Attaluri, Nithya, Iturrate, Iñaki, Liu, Ruibo, Li, Yunxuan, Cogan, Sarah, Chen, Jeremy, Jia, Chao, Gu, Chenjie, Zhang, Qiao, Grimstad, Jordan, Hartman, Ale Jakse, Garcia, Xavier, Pillai, Thanumalayan Sankaranarayana, Devlin, Jacob, Laskin, Michael, Casas, Diego de Las, Valter, Dasha, Tao, Connie, Blanco, Lorenzo, Badia, Adrià Puigdomènech, Reitter, David, Chen, Mianna, Brennan, Jenny, Rivera, Clara, Brin, Sergey, Iqbal, Shariq, Surita, Gabriela, Labanowski, Jane, Rao, Abhi, Winkler, Stephanie, Parisotto, Emilio, Gu, Yiming, Olszewska, Kate, Addanki, Ravi, Miech, Antoine, Louis, Annie, Teplyashin, Denis, Brown, Geoff, Catt, Elliot, Balaguer, Jan, Xiang, Jackie, Wang, Pidong, Ashwood, Zoe, Briukhov, Anton, Webson, Albert, Ganapathy, Sanjay, Sanghavi, Smit, Kannan, Ajay, Chang, Ming-Wei, Stjerngren, Axel, Djolonga, Josip, Sun, Yuting, Bapna, Ankur, Aitchison, Matthew, Pejman, Pedram, Michalewski, Henryk, Yu, Tianhe, Wang, Cindy, Love, Juliette, Ahn, Junwhan, Bloxwich, Dawn, Han, Kehang, Humphreys, Peter, Sellam, Thibault, Bradbury, James, Godbole, Varun, Samangooei, Sina, Damoc, Bogdan, Kaskasoli, Alex, Arnold, Sébastien M. R., Vasudevan, Vijay, Agrawal, Shubham, Riesa, Jason, Lepikhin, Dmitry, Tanburn, Richard, Srinivasan, Srivatsan, Lim, Hyeontaek, Hodkinson, Sarah, Shyam, Pranav, Ferret, Johan, Hand, Steven, Garg, Ankush, Paine, Tom Le, Li, Jian, Li, Yujia, Giang, Minh, Neitz, Alexander, Abbas, Zaheer, York, Sarah, Reid, Machel, Cole, Elizabeth, Chowdhery, Aakanksha, Das, Dipanjan, Rogozińska, Dominika, Nikolaev, Vitaliy, Sprechmann, Pablo, Nado, Zachary, Zilka, Lukas, Prost, Flavien, He, Luheng, Monteiro, Marianne, Mishra, Gaurav, Welty, Chris, Newlan, Josh, Jia, Dawei, Allamanis, Miltiadis, Hu, Clara Huiyi, de Liedekerke, Raoul, Gilmer, Justin, Saroufim, Carl, Rijhwani, Shruti, Hou, Shaobo, Shrivastava, Disha, Baddepudi, Anirudh, Goldin, Alex, Ozturel, Adnan, Cassirer, Albin, Xu, Yunhan, Sohn, Daniel, Sachan, Devendra, Amplayo, Reinald Kim, Swanson, Craig, Petrova, Dessie, Narayan, Shashi, Guez, Arthur, Brahma, Siddhartha, Landon, Jessica, Patel, Miteyan, Zhao, Ruizhe, Villela, Kevin, Wang, Luyu, Jia, Wenhao, Rahtz, Matthew, Giménez, Mai, Yeung, Legg, Keeling, James, Georgiev, Petko, Mincu, Diana, Wu, Boxi, Haykal, Salem, Saputro, Rachel, Vodrahalli, Kiran, Qin, James, Cankara, Zeynep, Sharma, Abhanshu, Fernando, Nick, Hawkins, Will, Neyshabur, Behnam, Kim, Solomon, Hutter, Adrian, Agrawal, Priyanka, Castro-Ros, Alex, Driessche, George van den, Wang, Tao, Yang, Fan, Chang, Shuo-yiin, Komarek, Paul, McIlroy, Ross, Lučić, Mario, Zhang, Guodong, Farhan, Wael, Sharman, Michael, Natsev, Paul, Michel, Paul, Bansal, Yamini, Qiao, Siyuan, Cao, Kris, Shakeri, Siamak, Butterfield, Christina, Chung, Justin, Rubenstein, Paul Kishan, Agrawal, Shivani, Mensch, Arthur, Soparkar, Kedar, Lenc, Karel, Chung, Timothy, Pope, Aedan, Maggiore, Loren, Kay, Jackie, Jhakra, Priya, Wang, Shibo, Maynez, Joshua, Phuong, Mary, Tobin, Taylor, Tacchetti, Andrea, Trebacz, Maja, Robinson, Kevin, Katariya, Yash, Riedel, Sebastian, Bailey, Paige, Xiao, Kefan, Ghelani, Nimesh, Aroyo, Lora, Slone, Ambrose, Houlsby, Neil, Xiong, Xuehan, Yang, Zhen, Gribovskaya, Elena, Adler, Jonas, Wirth, Mateo, Lee, Lisa, Li, Music, Kagohara, Thais, Pavagadhi, Jay, Bridgers, Sophie, Bortsova, Anna, Ghemawat, Sanjay, Ahmed, Zafarali, Liu, Tianqi, Powell, Richard, Bolina, Vijay, Iinuma, Mariko, Zablotskaia, Polina, Besley, James, Chung, Da-Woon, Dozat, Timothy, Comanescu, Ramona, Si, Xiance, Greer, Jeremy, Su, Guolong, Polacek, Martin, Kaufman, Raphaël Lopez, Tokumine, Simon, Hu, Hexiang, Buchatskaya, Elena, Miao, Yingjie, Elhawaty, Mohamed, Siddhant, Aditya, Tomasev, Nenad, Xing, Jinwei, Greer, Christina, Miller, Helen, Ashraf, Shereen, Roy, Aurko, Zhang, Zizhao, Ma, Ada, Filos, Angelos, Besta, Milos, Blevins, Rory, Klimenko, Ted, Yeh, Chih-Kuan, Changpinyo, Soravit, Mu, Jiaqi, Chang, Oscar, Pajarskas, Mantas, Muir, Carrie, Cohen, Vered, Lan, Charline Le, Haridasan, Krishna, Marathe, Amit, Hansen, Steven, Douglas, Sholto, Samuel, Rajkumar, Wang, Mingqiu, Austin, Sophia, Lan, Chang, Jiang, Jiepu, Chiu, Justin, Lorenzo, Jaime Alonso, Sjösund, Lars Lowe, Cevey, Sébastien, Gleicher, Zach, Avrahami, Thi, Boral, Anudhyan, Srinivasan, Hansa, Selo, Vittorio, May, Rhys, Aisopos, Konstantinos, Hussenot, Léonard, Soares, Livio Baldini, Baumli, Kate, Chang, Michael B., Recasens, Adrià, Caine, Ben, Pritzel, Alexander, Pavetic, Filip, Pardo, Fabio, Gergely, Anita, Frye, Justin, Ramasesh, Vinay, Horgan, Dan, Badola, Kartikeya, Kassner, Nora, Roy, Subhrajit, Dyer, Ethan, Campos, Víctor Campos, Tomala, Alex, Tang, Yunhao, Badawy, Dalia El, White, Elspeth, Mustafa, Basil, Lang, Oran, Jindal, Abhishek, Vikram, Sharad, Gong, Zhitao, Caelles, Sergi, Hemsley, Ross, Thornton, Gregory, Feng, Fangxiaoyu, Stokowiec, Wojciech, Zheng, Ce, Thacker, Phoebe, Ünlü, Çağlar, Zhang, Zhishuai, Saleh, Mohammad, Svensson, James, Bileschi, Max, Patil, Piyush, Anand, Ankesh, Ring, Roman, Tsihlas, Katerina, Vezer, Arpi, Selvi, Marco, Shevlane, Toby, Rodriguez, Mikel, Kwiatkowski, Tom, Daruki, Samira, Rong, Keran, Dafoe, Allan, FitzGerald, Nicholas, Gu-Lemberg, Keren, Khan, Mina, Hendricks, Lisa Anne, Pellat, Marie, Feinberg, Vladimir, Cobon-Kerr, James, Sainath, Tara, Rauh, Maribeth, Hashemi, Sayed Hadi, Ives, Richard, Hasson, Yana, Noland, Eric, Cao, Yuan, Byrd, Nathan, Hou, Le, Wang, Qingze, Sottiaux, Thibault, Paganini, Michela, Lespiau, Jean-Baptiste, Moufarek, Alexandre, Hassan, Samer, Shivakumar, Kaushik, van Amersfoort, Joost, Mandhane, Amol, Joshi, Pratik, Goyal, Anirudh, Tung, Matthew, Brock, Andrew, Sheahan, Hannah, Misra, Vedant, Li, Cheng, Rakićević, Nemanja, Dehghani, Mostafa, Liu, Fangyu, Mittal, Sid, Oh, Junhyuk, Noury, Seb, Sezener, Eren, Huot, Fantine, Lamm, Matthew, De Cao, Nicola, Chen, Charlie, Mudgal, Sidharth, Stella, Romina, Brooks, Kevin, Vasudevan, Gautam, Liu, Chenxi, Chain, Mainak, Melinkeri, Nivedita, Cohen, Aaron, Wang, Venus, Seymore, Kristie, Zubkov, Sergey, Goel, Rahul, Yue, Summer, Krishnakumaran, Sai, Albert, Brian, Hurley, Nate, Sano, Motoki, Mohananey, Anhad, Joughin, Jonah, Filonov, Egor, Kępa, Tomasz, Eldawy, Yomna, Lim, Jiawern, Rishi, Rahul, Badiezadegan, Shirin, Bos, Taylor, Chang, Jerry, Jain, Sanil, Padmanabhan, Sri Gayatri Sundara, Puttagunta, Subha, Krishna, Kalpesh, Baker, Leslie, Kalb, Norbert, Bedapudi, Vamsi, Kurzrok, Adam, Lei, Shuntong, Yu, Anthony, Litvin, Oren, Zhou, Xiang, Wu, Zhichun, Sobell, Sam, Siciliano, Andrea, Papir, Alan, Neale, Robby, Bragagnolo, Jonas, Toor, Tej, Chen, Tina, Anklin, Valentin, Wang, Feiran, Feng, Richie, Gholami, Milad, Ling, Kevin, Liu, Lijuan, Walter, Jules, Moghaddam, Hamid, Kishore, Arun, Adamek, Jakub, Mercado, Tyler, Mallinson, Jonathan, Wandekar, Siddhinita, Cagle, Stephen, Ofek, Eran, Garrido, Guillermo, Lombriser, Clemens, Mukha, Maksim, Sun, Botu, Mohammad, Hafeezul Rahman, Matak, Josip, Qian, Yadi, Peswani, Vikas, Janus, Pawel, Yuan, Quan, Schelin, Leif, David, Oana, Garg, Ankur, He, Yifan, Duzhyi, Oleksii, Älgmyr, Anton, Lottaz, Timothée, Li, Qi, Yadav, Vikas, Xu, Luyao, Chinien, Alex, Shivanna, Rakesh, Chuklin, Aleksandr, Li, Josie, Spadine, Carrie, Wolfe, Travis, Mohamed, Kareem, Das, Subhabrata, Dai, Zihang, He, Kyle, von Dincklage, Daniel, Upadhyay, Shyam, Maurya, Akanksha, Chi, Luyan, Krause, Sebastian, Salama, Khalid, Rabinovitch, Pam G, M, Pavan Kumar Reddy, Selvan, Aarush, Dektiarev, Mikhail, Ghiasi, Golnaz, Guven, Erdem, Gupta, Himanshu, Liu, Boyi, Sharma, Deepak, Shtacher, Idan Heimlich, Paul, Shachi, Akerlund, Oscar, Aubet, François-Xavier, Huang, Terry, Zhu, Chen, Zhu, Eric, Teixeira, Elico, Fritze, Matthew, Bertolini, Francesco, Marinescu, Liana-Eleonora, Bölle, Martin, Paulus, Dominik, Gupta, Khyatti, Latkar, Tejasi, Chang, Max, Sanders, Jason, Wilson, Roopa, Wu, Xuewei, Tan, Yi-Xuan, Thiet, Lam Nguyen, Doshi, Tulsee, Lall, Sid, Mishra, Swaroop, Chen, Wanming, Luong, Thang, Benjamin, Seth, Lee, Jasmine, Andrejczuk, Ewa, Rabiej, Dominik, Ranjan, Vipul, Styrc, Krzysztof, Yin, Pengcheng, Simon, Jon, Harriott, Malcolm Rose, Bansal, Mudit, Robsky, Alexei, Bacon, Geoff, Greene, David, Mirylenka, Daniil, Zhou, Chen, Sarvana, Obaid, Goyal, Abhimanyu, Andermatt, Samuel, Siegler, Patrick, Horn, Ben, Israel, Assaf, Pongetti, Francesco, Chen, Chih-Wei "Louis", Selvatici, Marco, Silva, Pedro, Wang, Kathie, Tolins, Jackson, Guu, Kelvin, Yogev, Roey, Cai, Xiaochen, Agostini, Alessandro, Shah, Maulik, Nguyen, Hung, Donnaile, Noah Ó, Pereira, Sébastien, Friso, Linda, Stambler, Adam, Kuang, Chenkai, Romanikhin, Yan, Geller, Mark, Yan, ZJ, Jang, Kane, Lee, Cheng-Chun, Fica, Wojciech, Malmi, Eric, Tan, Qijun, Banica, Dan, Balle, Daniel, Pham, Ryan, Huang, Yanping, Avram, Diana, Shi, Hongzhi, Singh, Jasjot, Hidey, Chris, Ahuja, Niharika, Saxena, Pranab, Dooley, Dan, Potharaju, Srividya Pranavi, O'Neill, Eileen, Gokulchandran, Anand, Foley, Ryan, Zhao, Kai, Dusenberry, Mike, Liu, Yuan, Mehta, Pulkit, Kotikalapudi, Ragha, Safranek-Shrader, Chalence, Goodman, Andrew, Kessinger, Joshua, Globen, Eran, Kolhar, Prateek, Gorgolewski, Chris, Ibrahim, Ali, Song, Yang, Eichenbaum, Ali, Brovelli, Thomas, Potluri, Sahitya, Lahoti, Preethi, Baetu, Cip, Ghorbani, Ali, Chen, Charles, Crawford, Andy, Pal, Shalini, Sridhar, Mukund, Gurita, Petru, Mujika, Asier, Petrovski, Igor, Cedoz, Pierre-Louis, Li, Chenmei, Chen, Shiyuan, Santo, Niccolò Dal, Goyal, Siddharth, Punjabi, Jitesh, Kappaganthu, Karthik, Kwak, Chester, LV, Pallavi, Velury, Sarmishta, Choudhury, Himadri, Hall, Jamie, Shah, Premal, Figueira, Ricardo, Thomas, Matt, Lu, Minjie, Zhou, Ting, Kumar, Chintu, Jurdi, Thomas, Chikkerur, Sharat, Ma, Yenai, Yu, Adams, Kwak, Soo, Ähdel, Victor, Rajayogam, Sujeevan, Choma, Travis, Liu, Fei, Barua, Aditya, Ji, Colin, Park, Ji Ho, Hellendoorn, Vincent, Bailey, Alex, Bilal, Taylan, Zhou, Huanjie, Khatir, Mehrdad, Sutton, Charles, Rzadkowski, Wojciech, Macintosh, Fiona, Shagin, Konstantin, Medina, Paul, Liang, Chen, Zhou, Jinjing, Shah, Pararth, Bi, Yingying, Dankovics, Attila, Banga, Shipra, Lehmann, Sabine, Bredesen, Marissa, Lin, Zifan, Hoffmann, John Eric, Lai, Jonathan, Chung, Raynald, Yang, Kai, Balani, Nihal, Bražinskas, Arthur, Sozanschi, Andrei, Hayes, Matthew, Alcalde, Héctor Fernández, Makarov, Peter, Chen, Will, Stella, Antonio, Snijders, Liselotte, Mandl, Michael, Kärrman, Ante, Nowak, Paweł, Wu, Xinyi, Dyck, Alex, Vaidyanathan, Krishnan, R, Raghavender, Mallet, Jessica, Rudominer, Mitch, Johnston, Eric, Mittal, Sushil, Udathu, Akhil, Christensen, Janara, Verma, Vishal, Irving, Zach, Santucci, Andreas, Elsayed, Gamaleldin, Davoodi, Elnaz, Georgiev, Marin, Tenney, Ian, Hua, Nan, Cideron, Geoffrey, Leurent, Edouard, Alnahlawi, Mahmoud, Georgescu, Ionut, Wei, Nan, Zheng, Ivy, Scandinaro, Dylan, Jiang, Heinrich, Snoek, Jasper, Sundararajan, Mukund, Wang, Xuezhi, Ontiveros, Zack, Karo, Itay, Cole, Jeremy, Rajashekhar, Vinu, Tumeh, Lara, Ben-David, Eyal, Jain, Rishub, Uesato, Jonathan, Datta, Romina, Bunyan, Oskar, Wu, Shimu, Zhang, John, Stanczyk, Piotr, Zhang, Ye, Steiner, David, Naskar, Subhajit, Azzam, Michael, Johnson, Matthew, Paszke, Adam, Chiu, Chung-Cheng, Elias, Jaume Sanchez, Mohiuddin, Afroz, Muhammad, Faizan, Miao, Jin, Lee, Andrew, Vieillard, Nino, Park, Jane, Zhang, Jiageng, Stanway, Jeff, Garmon, Drew, Karmarkar, Abhijit, Dong, Zhe, Lee, Jong, Kumar, Aviral, Zhou, Luowei, Evens, Jonathan, Isaac, William, Irving, Geoffrey, Loper, Edward, Fink, Michael, Arkatkar, Isha, Chen, Nanxin, Shafran, Izhak, Petrychenko, Ivan, Chen, Zhe, Jia, Johnson, Levskaya, Anselm, Zhu, Zhenkai, Grabowski, Peter, Mao, Yu, Magni, Alberto, Yao, Kaisheng, Snaider, Javier, Casagrande, Norman, Palmer, Evan, Suganthan, Paul, Castaño, Alfonso, Giannoumis, Irene, Kim, Wooyeol, Rybiński, Mikołaj, Sreevatsa, Ashwin, Prendki, Jennifer, Soergel, David, Goedeckemeyer, Adrian, Gierke, Willi, Jafari, Mohsen, Gaba, Meenu, Wiesner, Jeremy, Wright, Diana Gage, Wei, Yawen, Vashisht, Harsha, Kulizhskaya, Yana, Hoover, Jay, Le, Maigo, Li, Lu, Iwuanyanwu, Chimezie, Liu, Lu, Ramirez, Kevin, Khorlin, Andrey, Cui, Albert, LIN, Tian, Wu, Marcus, Aguilar, Ricardo, Pallo, Keith, Chakladar, Abhishek, Perng, Ginger, Abellan, Elena Allica, Zhang, Mingyang, Dasgupta, Ishita, Kushman, Nate, Penchev, Ivo, Repina, Alena, Wu, Xihui, van der Weide, Tom, Ponnapalli, Priya, Kaplan, Caroline, Simsa, Jiri, Li, Shuangfeng, Dousse, Olivier, Piper, Jeff, Ie, Nathan, Pasumarthi, Rama, Lintz, Nathan, Vijayakumar, Anitha, Andor, Daniel, Valenzuela, Pedro, Lui, Minnie, Paduraru, Cosmin, Peng, Daiyi, Lee, Katherine, Zhang, Shuyuan, Greene, Somer, Nguyen, Duc Dung, Kurylowicz, Paula, Hardin, Cassidy, Dixon, Lucas, Janzer, Lili, Choo, Kiam, Feng, Ziqiang, Zhang, Biao, Singhal, Achintya, Du, Dayou, McKinnon, Dan, Antropova, Natasha, Bolukbasi, Tolga, Keller, Orgad, Reid, David, Finchelstein, Daniel, Raad, Maria Abi, Crocker, Remi, Hawkins, Peter, Dadashi, Robert, Gaffney, Colin, Franko, Ken, Bulanova, Anna, Leblond, Rémi, Chung, Shirley, Askham, Harry, Cobo, Luis C., Xu, Kelvin, Fischer, Felix, Xu, Jun, Sorokin, Christina, Alberti, Chris, Lin, Chu-Cheng, Evans, Colin, Dimitriev, Alek, Forbes, Hannah, Banarse, Dylan, Tung, Zora, Omernick, Mark, Bishop, Colton, Sterneck, Rachel, Jain, Rohan, Xia, Jiawei, Amid, Ehsan, Piccinno, Francesco, Wang, Xingyu, Banzal, Praseem, Mankowitz, Daniel J., Polozov, Alex, Krakovna, Victoria, Brown, Sasha, Bateni, MohammadHossein, Duan, Dennis, Firoiu, Vlad, Thotakuri, Meghana, Natan, Tom, Geist, Matthieu, Girgin, Ser tan, Li, Hui, Ye, Jiayu, Roval, Ofir, Tojo, Reiko, Kwong, Michael, Lee-Thorp, James, Yew, Christopher, Sinopalnikov, Danila, Ramos, Sabela, Mellor, John, Sharma, Abhishek, Wu, Kathy, Miller, David, Sonnerat, Nicolas, Vnukov, Denis, Greig, Rory, Beattie, Jennifer, Caveness, Emily, Bai, Libin, Eisenschlos, Julian, Korchemniy, Alex, Tsai, Tomy, Jasarevic, Mimi, Kong, Weize, Dao, Phuong, Zheng, Zeyu, Liu, Frederick, Zhu, Rui, Teh, Tian Huey, Sanmiya, Jason, Gladchenko, Evgeny, Trdin, Nejc, Toyama, Daniel, Rosen, Evan, Tavakkol, Sasan, Xue, Linting, Elkind, Chen, Woodman, Oliver, Carpenter, John, Papamakarios, George, Kemp, Rupert, Kafle, Sushant, Grunina, Tanya, Sinha, Rishika, Talbert, Alice, Wu, Diane, Owusu-Afriyie, Denese, Thornton, Chloe, Pont-Tuset, Jordi, Narayana, Pradyumna, Li, Jing, Fatehi, Saaber, Wieting, John, Ajmeri, Omar, Uria, Benigno, Ko, Yeongil, Knight, Laura, Héliou, Amélie, Niu, Ning, Gu, Shane, Pang, Chenxi, Li, Yeqing, Levine, Nir, Stolovich, Ariel, Santamaria-Fernandez, Rebeca, Goenka, Sonam, Yustalim, Wenny, Strudel, Robin, Elqursh, Ali, Deck, Charlie, Lee, Hyo, Li, Zonglin, Levin, Kyle, Hoffmann, Raphael, Holtmann-Rice, Dan, Bachem, Olivier, Arora, Sho, Koh, Christy, Yeganeh, Soheil Hassas, Põder, Siim, Tariq, Mukarram, Sun, Yanhua, Ionita, Lucian, Seyedhosseini, Mojtaba, Tafti, Pouya, Liu, Zhiyu, Gulati, Anmol, Liu, Jasmine, Ye, Xinyu, Chrzaszcz, Bart, Wang, Lily, Sethi, Nikhil, Li, Tianrun, Brown, Ben, Singh, Shreya, Fan, Wei, Parisi, Aaron, Stanton, Joe, Koverkathu, Vinod, Choquette-Choo, Christopher A., Li, Yunjie, Lu, TJ, Shroff, Prakash, Varadarajan, Mani, Bahargam, Sanaz, Willoughby, Rob, Gaddy, David, Desjardins, Guillaume, Cornero, Marco, Robenek, Brona, Mittal, Bhavishya, Albrecht, Ben, Shenoy, Ashish, Moiseev, Fedor, Jacobsson, Henrik, Ghaffarkhah, Alireza, Rivière, Morgane, Walton, Alanna, Crepy, Clément, Parrish, Alicia, Zhou, Zongwei, Farabet, Clement, Radebaugh, Carey, Srinivasan, Praveen, van der Salm, Claudia, Fidjeland, Andreas, Scellato, Salvatore, Latorre-Chimoto, Eri, Klimczak-Plucińska, Hanna, Bridson, David, de Cesare, Dario, Hudson, Tom, Mendolicchio, Piermaria, Walker, Lexi, Morris, Alex, Mauger, Matthew, Guseynov, Alexey, Reid, Alison, Odoom, Seth, Loher, Lucia, Cotruta, Victor, Yenugula, Madhavi, Grewe, Dominik, Petrushkina, Anastasia, Duerig, Tom, Sanchez, Antonio, Yadlowsky, Steve, Shen, Amy, Globerson, Amir, Webb, Lynette, Dua, Sahil, Li, Dong, Bhupatiraju, Surya, Hurt, Dan, Qureshi, Haroon, Agarwal, Ananth, Shani, Tomer, Eyal, Matan, Khare, Anuj, Belle, Shreyas Rammohan, Wang, Lei, Tekur, Chetan, Kale, Mihir Sanjay, Wei, Jinliang, Sang, Ruoxin, Saeta, Brennan, Liechty, Tyler, Sun, Yi, Zhao, Yao, Lee, Stephan, Nayak, Pandu, Fritz, Doug, Vuyyuru, Manish Reddy, Aslanides, John, Vyas, Nidhi, Wicke, Martin, Ma, Xiao, Eltyshev, Evgenii, Martin, Nina, Cate, Hardie, Manyika, James, Amiri, Keyvan, Kim, Yelin, Xiong, Xi, Kang, Kai, Luisier, Florian, Tripuraneni, Nilesh, Madras, David, Guo, Mandy, Waters, Austin, Wang, Oliver, Ainslie, Joshua, Baldridge, Jason, Zhang, Han, Pruthi, Garima, Bauer, Jakob, Yang, Feng, Mansour, Riham, Gelman, Jason, Xu, Yang, Polovets, George, Liu, Ji, Cai, Honglong, Chen, Warren, Sheng, XiangHai, Xue, Emily, Ozair, Sherjil, Angermueller, Christof, Li, Xiaowei, Sinha, Anoop, Wang, Weiren, Wiesinger, Julia, Koukoumidis, Emmanouil, Tian, Yuan, Iyer, Anand, Gurumurthy, Madhu, Goldenson, Mark, Shah, Parashar, Blake, MK, Yu, Hongkun, Urbanowicz, Anthony, Palomaki, Jennimaria, Fernando, Chrisantha, Durden, Ken, Mehta, Harsh, Momchev, Nikola, Rahimtoroghi, Elahe, Georgaki, Maria, Raul, Amit, Ruder, Sebastian, Redshaw, Morgan, Lee, Jinhyuk, Zhou, Denny, Jalan, Komal, Li, Dinghua, Hechtman, Blake, Schuh, Parker, Nasr, Milad, Milan, Kieran, Mikulik, Vladimir, Franco, Juliana, Green, Tim, Nguyen, Nam, Kelley, Joe, Mahendru, Aroma, Hu, Andrea, Howland, Joshua, Vargas, Ben, Hui, Jeffrey, Bansal, Kshitij, Rao, Vikram, Ghiya, Rakesh, Wang, Emma, Ye, Ke, Sarr, Jean Michel, Preston, Melanie Moranski, Elish, Madeleine, Li, Steve, Kaku, Aakash, Gupta, Jigar, Pasupat, Ice, Juan, Da-Cheng, Someswar, Milan, M., Tejvi, Chen, Xinyun, Amini, Aida, Fabrikant, Alex, Chu, Eric, Dong, Xuanyi, Muthal, Amruta, Buthpitiya, Senaka, Jauhari, Sarthak, Khandelwal, Urvashi, Hitron, Ayal, Ren, Jie, Rinaldi, Larissa, Drath, Shahar, Dabush, Avigail, Jiang, Nan-Jiang, Godhia, Harshal, Sachs, Uli, Chen, Anthony, Fan, Yicheng, Taitelbaum, Hagai, Noga, Hila, Dai, Zhuyun, Wang, James, Hamer, Jenny, Ferng, Chun-Sung, Elkind, Chenel, Atias, Aviel, Lee, Paulina, Listík, Vít, Carlen, Mathias, van de Kerkhof, Jan, Pikus, Marcin, Zaher, Krunoslav, Müller, Paul, Zykova, Sasha, Stefanec, Richard, Gatsko, Vitaly, Hirnschall, Christoph, Sethi, Ashwin, Xu, Xingyu Federico, Ahuja, Chetan, Tsai, Beth, Stefanoiu, Anca, Feng, Bo, Dhandhania, Keshav, Katyal, Manish, Gupta, Akshay, Parulekar, Atharva, Pitta, Divya, Zhao, Jing, Bhatia, Vivaan, Bhavnani, Yashodha, Alhadlaq, Omar, Li, Xiaolin, Danenberg, Peter, Tu, Dennis, Pine, Alex, Filippova, Vera, Ghosh, Abhipso, Limonchik, Ben, Urala, Bhargava, Lanka, Chaitanya Krishna, Clive, Derik, Li, Edward, Wu, Hao, Hongtongsak, Kevin, Li, Ianna, Thakkar, Kalind, Omarov, Kuanysh, Majmundar, Kushal, Alverson, Michael, Kucharski, Michael, Patel, Mohak, Jain, Mudit, Zabelin, Maksim, Pelagatti, Paolo, Kohli, Rohan, Kumar, Saurabh, Kim, Joseph, Sankar, Swetha, Shah, Vineet, Ramachandruni, Lakshmi, Zeng, Xiangkai, Bariach, Ben, Weidinger, Laura, Vu, Tu, Andreev, Alek, He, Antoine, Hui, Kevin, Kashem, Sheleem, Subramanya, Amar, Hsiao, Sissie, Hassabis, Demis, Kavukcuoglu, Koray, Sadovsky, Adam, Le, Quoc, Strohman, Trevor, Wu, Yonghui, Petrov, Slav, Dean, Jeffrey, and Vinyals, Oriol

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition
Abstract

This report introduces a new family of multimodal models, Gemini, that exhibit remarkable capabilities across image, audio, video, and text understanding. The Gemini family consists of Ultra, Pro, and Nano sizes, suitable for applications ranging from complex reasoning tasks to on-device memory-constrained use-cases. Evaluation on a broad range of benchmarks shows that our most-capable Gemini Ultra model advances the state of the art in 30 of 32 of these benchmarks - notably being the first model to achieve human-expert performance on the well-studied exam benchmark MMLU, and improving the state of the art in every one of the 20 multimodal benchmarks we examined. We believe that the new capabilities of the Gemini family in cross-modal reasoning and language understanding will enable a wide variety of use cases. We discuss our approach toward post-training and deploying Gemini models responsibly to users through services including Gemini, Gemini Advanced, Google AI Studio, and Cloud Vertex AI.

Published
2023

27. Chromatin binding by HORMAD proteins regulates meiotic recombination initiation

Author

Milano, Carolyn R, Ur, Sarah N, Gu, Yajie, Zhang, Jessie, Allison, Rachal, Brown, George, Neale, Matthew J, Tromer, Eelco C, Corbett, Kevin D, and Hochwagen, Andreas

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Meiosis, Nucleosomes, Cryoelectron Microscopy, Phylogeny, Saccharomyces cerevisiae, DNA, Nuclear Proteins, Saccharomyces cerevisiae Proteins, Budding Yeast, Chromatin, Chromosome Segregation, HORMA, Information and Computing Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The meiotic chromosome axis coordinates chromosome organization and interhomolog recombination in meiotic prophase and is essential for fertility. In S. cerevisiae, the HORMAD protein Hop1 mediates the enrichment of axis proteins at nucleosome-rich islands through a central chromatin-binding region (CBR). Here, we use cryoelectron microscopy to show that the Hop1 CBR directly recognizes bent nucleosomal DNA through a composite interface in its PHD and winged helix-turn-helix domains. Targeted disruption of the Hop1 CBR-nucleosome interface causes a localized reduction of axis protein binding and meiotic DNA double-strand breaks (DSBs) in axis islands and leads to defects in chromosome synapsis. Synthetic effects with mutants of the Hop1 regulator Pch2 suggest that nucleosome binding delays a conformational switch in Hop1 from a DSB-promoting, Pch2-inaccessible state to a DSB-inactive, Pch2-accessible state to regulate the extent of meiotic DSB formation. Phylogenetic analyses of meiotic HORMADs reveal an ancient origin of the CBR, suggesting that the mechanisms we uncover are broadly conserved.

Published
2024

28. Associations of plasma neurofilament light chain with cognition and neuroimaging measures in community-dwelling early old age men

Author

Tang, Rongxiang, Buchholz, Erik, Dale, Anders M, Rissman, Robert A, Fennema-Notestine, Christine, Gillespie, Nathan A, Hagler, Donald J, Lyons, Michael J, Neale, Michael C, Panizzon, Matthew S, Puckett, Olivia K, Reynolds, Chandra A, Franz, Carol E, Kremen, William S, and Elman, Jeremy A

Subjects
Biomedical and Clinical Sciences, Health Sciences, Brain Disorders, Mental Health, Health Disparities, Prevention, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Neurodegenerative, Dementia, Acquired Cognitive Impairment, Basic Behavioral and Social Science, Clinical Research, Neurosciences, Alzheimer's Disease, Behavioral and Social Science, Mind and Body, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Mental health, Humans, Male, Neurofilament Proteins, Aged, Middle Aged, Independent Living, Cross-Sectional Studies, Cognitive Dysfunction, Neuroimaging, Cognition, Biomarkers, Neuropsychological Tests, Magnetic Resonance Imaging, Brain, White Matter, Neurofilament light chain, White matter hyperintensity, Processing speed, Neurodegeneration, Blood-based biomarkers, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundPlasma neurofilament light chain (NfL) is a promising biomarker of neurodegeneration with potential clinical utility in monitoring the progression of neurodegenerative diseases. However, the cross-sectional associations of plasma NfL with measures of cognition and brain have been inconsistent in community-dwelling populations.MethodsWe examined these associations in a large community-dwelling sample of early old age men (N = 969, mean age = 67.57 years, range = 61-73 years), who are either cognitively unimpaired (CU) or with mild cognitive impairment (MCI). Specifically, we investigated five cognitive domains (executive function, episodic memory, verbal fluency, processing speed, visual-spatial ability), as well as neuroimaging measures of gray and white matter.ResultsAfter adjusting for age, health status, and young adult general cognitive ability, plasma NfL level was only significantly associated with processing speed and white matter hyperintensity (WMH) volume, but not with other cognitive or neuroimaging measures. The association with processing speed was driven by individuals with MCI, as it was not detected in CU individuals.ConclusionsThese results suggest that in early old age men without dementia, plasma NfL does not appear to be sensitive to cross-sectional individual differences in most domains of cognition or neuroimaging measures of gray and white matter. The revealed plasma NfL associations were limited to WMH for all participants and processing speed only within the MCI cohort. Importantly, considering cognitive status in community-based samples will better inform the interpretation of the relationships of plasma NfL with cognition and brain and may help resolve mixed findings in the literature.

Published
2024

29. Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment

Author

Madronich, S., Bernhard, G. H., Neale, P. J., Heikkilä, A., Andersen, M. P. Sulbæk, Andrady, A. L., Aucamp, P. J., Bais, A. F., Banaszak, A. T., Barnes, P. J., Bornman, J. F., Bruckman, L. S., Busquets, R., Chiodo, G., Häder, D.-P., Hanson, M. L., Hylander, S., Jansen, M. A. K., Lingham, G., Lucas, R. M., Calderon, R. Mackenzie, Olsen, C., Ossola, R., Pandey, K. K., Petropavlovskikh, I., Revell, L. E., Rhodes, L. E., Robinson, S. A., Robson, T. M., Rose, K. C., Schikowski, T., Solomon, K. R., Sulzberger, B., Wallington, T. J., Wang, Q.-W., Wängberg, S.-Å., White, C. C., Wilson, S. R., Zhu, L., and Neale, R. E.

Published
2024
Full Text
View/download PDF

30. Plastics in the environment in the context of UV radiation, climate change and the Montreal Protocol: UNEP Environmental Effects Assessment Panel, Update 2023

Author

Jansen, Marcel A. K., Andrady, Anthony L., Bornman, Janet F., Aucamp, Pieter J., Bais, Alkiviadis F., Banaszak, Anastazia T., Barnes, Paul W., Bernhard, Germar H., Bruckman, Laura S., Busquets, Rosa, Häder, Donat-P., Hanson, Mark L., Heikkilä, Anu M., Hylander, Samuel, Lucas, Robyn M., Mackenzie, Roy, Madronich, Sasha, Neale, Patrick J., Neale, Rachel E., Olsen, Catherine M., Ossola, Rachele, Pandey, Krishna K., Petropavlovskikh, Irina, Revell, Laura E., Robinson, Sharon A., Robson, T. Matthew, Rose, Kevin C., Solomon, Keith R., Andersen, Mads P. Sulbæk, Sulzberger, Barbara, Wallington, Timothy J., Wang, Qing-Wei, Wängberg, Sten-Åke, White, Christopher C., Young, Antony R., Zepp, Richard G., and Zhu, Liping

Published
2024
Full Text
View/download PDF

36. Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement

Author

LaFlamme, Christy W., Rastin, Cassandra, Sengupta, Soham, Pennington, Helen E., Russ-Hall, Sophie J., Schneider, Amy L., Bonkowski, Emily S., Almanza Fuerte, Edith P., Allan, Talia J., Zalusky, Miranda Perez-Galey, Goffena, Joy, Gibson, Sophia B., Nyaga, Denis M., Lieffering, Nico, Hebbar, Malavika, Walker, Emily V., Darnell, Daniel, Olsen, Scott R., Kolekar, Pandurang, Djekidel, Mohamed Nadhir, Rosikiewicz, Wojciech, McConkey, Haley, Kerkhof, Jennifer, Levy, Michael A., Relator, Raissa, Lev, Dorit, Lerman-Sagie, Tally, Park, Kristen L., Alders, Marielle, Cappuccio, Gerarda, Chatron, Nicolas, Demain, Leigh, Genevieve, David, Lesca, Gaetan, Roscioli, Tony, Sanlaville, Damien, Tedder, Matthew L., Gupta, Sachin, Jones, Elizabeth A., Weisz-Hubshman, Monika, Ketkar, Shamika, Dai, Hongzheng, Worley, Kim C., Rosenfeld, Jill A., Chao, Hsiao-Tuan, Neale, Geoffrey, Carvill, Gemma L., Wang, Zhaoming, Berkovic, Samuel F., Sadleir, Lynette G., Miller, Danny E., Scheffer, Ingrid E., Sadikovic, Bekim, and Mefford, Heather C.

Published
2024
Full Text
View/download PDF

40. A unified framework for estimating country-specific cumulative incidence for 18 diseases stratified by polygenic risk

Author

Jermy, Bradley, Läll, Kristi, Wolford, Brooke N., Wang, Ying, Zguro, Kristina, Cheng, Yipeng, Kanai, Masahiro, Kanoni, Stavroula, Yang, Zhiyu, Hartonen, Tuomo, Monti, Remo, Wanner, Julian, Youssef, Omar, Lippert, Christoph, van Heel, David, Okada, Yukinori, McCartney, Daniel L., Hayward, Caroline, Marioni, Riccardo E., Furini, Simone, Renieri, Alessandra, Martin, Alicia R., Neale, Benjamin M., Hveem, Kristian, Mägi, Reedik, Palotie, Aarno, Heyne, Henrike, Mars, Nina, Ganna, Andrea, and Ripatti, Samuli

Published
2024
Full Text
View/download PDF

42. Author Correction: Membrane lipids drive formation of KRAS4b-RAF1 RBDCRD nanoclusters on the membrane

Author

Shrestha, Rebika, Carpenter, Timothy S., Van, Que N., Agamasu, Constance, Tonelli, Marco, Aydin, Fikret, Chen, De, Gulten, Gulcin, Glosli, James N., López, Cesar A., Oppelstrup, Tomas, Neale, Chris, Gnanakaran, Sandrasegaram, Gillette, William K., Ingólfsson, Helgi I., Lightstone, Felice C., Stephen, Andrew G., Streitz, Frederick H., Nissley, Dwight V., and Turbyville, Thomas J.

Published
2024
Full Text
View/download PDF

43. Membrane lipids drive formation of KRAS4b-RAF1 RBDCRD nanoclusters on the membrane

Author

Shrestha, Rebika, Carpenter, Timothy S., Van, Que N., Agamasu, Constance, Tonelli, Marco, Aydin, Fikret, Chen, De, Gulten, Gulcin, Glosli, James N., López, Cesar A., Oppelstrup, Tomas, Neale, Chris, Gnanakaran, Sandrasegaram, Gillette, William K., Ingólfsson, Helgi I., Lightstone, Felice C., Stephen, Andrew G., Streitz, Frederick H., Nissley, Dwight V., and Turbyville, Thomas J.

Published
2024
Full Text
View/download PDF

47. Osmotic disruption of chromatin induces Topoisomerase 2 activity at sites of transcriptional stress

Author

William H. Gittens, Rachal M. Allison, Ellie M. Wright, George G. B. Brown, and Matthew J. Neale

Subjects
Science
Abstract

Abstract Transcription generates superhelical stress in DNA that poses problems for genome stability, but determining when and where such stress arises within chromosomes is challenging. Here, using G1-arrested S. cerevisiae cells, and employing rapid fixation and ultra-sensitive enrichment, we utilise the physiological activity of endogenous topoisomerase 2 (Top2) as a probe of transcription-induced superhelicity. We demonstrate that Top2 activity is surprisingly uncorrelated with transcriptional activity, suggesting that superhelical stress is obscured from Top2 within chromatin in vivo. We test this idea using osmotic perturbation—a treatment that transiently destabilises chromatin in vivo—revealing that Top2 activity redistributes within sub-minute timescales into broad zones patterned by long genes, convergent gene arrays, and transposon elements—and also by acute transcriptional induction. We propose that latent superhelical stress is normally absorbed by the intrinsic topological buffering capacity of chromatin, helping to avoid spurious topoisomerase activity arising within the essential coding regions of the genome.

Published
2024
Full Text
View/download PDF

48. Inpatient detoxification for alcohol and other drug use: qualitative study of patients’ accounts of their relationships with staff

Author

Joanne Neale, Beth Cairns, Kevin Gardiner, Wulf Livingston, Trevor McCarthy, and Andrew Perkins

Subjects
Detoxification, Inpatient, Substance use, Therapeutic alliance, Qualitative research, Medicine (General), R5-920, Social pathology. Social and public welfare. Criminology, HV1-9960
Abstract

Abstract Background The therapeutic alliance is an important predictor of treatment outcomes but people who use alcohol and other drugs report mixed views of treatment providers. We analysed patients’ accounts of inpatient detoxification staff to ascertain whether, and if so how, relationships with them, and thus the therapeutic alliance, might be improved. Methods Semi-structured qualitative interviews were conducted (in 2022/2023) with 20 people (14 males; 6 females) who had just completed inpatient detoxification in sixteen different facilities. Interviews were part of a larger longitudinal qualitative evaluation of an initiative to increase inpatient detoxification capacity across England. Results Patients described how treatment was delivered by professionals with diverse roles. They rated staff highly and appreciated their personal qualities; the standard of medical care and non-medical services they provided; their willingness to provide privacy, freedom and choice; the support given at key points in the treatment journey; and the positive impact staff relationships had on their substance use and lives more generally. Criticisms of staff were infrequent, mostly related to specific individuals or events, and potentially more common when detoxification occurred within general hospitals rather than within specialist services. Conclusions Patients’ accounts of staff in this study were more positive than documented in previous literature. However, the characteristics that patients appreciated (and disliked) were consistent with earlier research. There was scope to improve in some services and patient groups not interviewed may have held more negative views of staff. Overall, the holistic and patient-centred approach that staff adopted, and patients valued, appears to contribute to a good therapeutic alliance.

Published
2024
Full Text
View/download PDF

50. Exploring the X-Factor: Generation X Public School Principals and Assistant Principals Experience Leading a Multigenerational Workforce

Author

Katreca N. Reed Neale

Abstract

There is a shortage of literature containing the principal's voice and articulation of her or his journey through leadership. This exploratory research extends the understanding of the nature and meaning of the lived experiences of the Generation X cohort within the context of school principals and assistant principals leading in 21st century schools. This qualitative hermeneutic phenomenological study explored Generation X school principals' and assistant principals' experiences leading a multigenerational workforce. A multigenerational workforce is defined as comprising of employees from five different generations: Traditionalists, Baby Boomers, Generation X, Millennials, and Generation Z. The researcher sought to explore (a) what aspects of Generation X school principal and assistant principal education, training, or development helped them prepare as a school leader; (b) how Generation X school principals and assistant principals describe and enact their leadership style(s) to lead a multigenerational workforce; and (c) how societal context has influenced Generation X principal and assistant principal leadership (i.e., Global Pandemic, social and emotional health concerns). Three global themes emerged from semi-structured interviews with 15 Generation X school principals and assistant principals in a public school district: Identity, Flexibility and Adaptability, and Social Awareness. The findings indicate (a) participant identity for these participants is multifaceted and informed by culture and social interactions, (b) Generation X leaders are flexible and adaptable, and (c) Generation X leaders utilize social awareness and societal context to foster equitable and inclusive learning environments. This research highlights the experiences of an often overlooked generation to help these Generation X leaders reflect on the ways their adolescent experiences influence the way they currently lead a multigenerational workforce. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Published
2024

Catalog

Books, media, physical & digital resources
See catalog results