235 research outputs found
Kani: A Lightweight and Highly Hackable Framework for Building Language Model Applications
Language model applications are becoming increasingly popular and complex,
often including features like tool usage and retrieval augmentation. However,
existing frameworks for such applications are often opinionated, deciding for
developers how their prompts ought to be formatted and imposing limitations on
customizability and reproducibility. To solve this we present Kani: a
lightweight, flexible, and model-agnostic open-source framework for building
language model applications. Kani helps developers implement a variety of
complex features by supporting the core building blocks of chat interaction:
model interfacing, chat management, and robust function calling. All Kani core
functions are easily overridable and well documented to empower developers to
customize functionality for their own needs. Kani thus serves as a useful tool
for researchers, hobbyists, and industry professionals alike to accelerate
their development while retaining interoperability and fine-grained control.Comment: In submission to NLP-OS
An H4K16 histone acetyltransferase mediates decondensation of the X chromosome in C. elegans males
Abstract
Background
In C. elegans, in order to equalize gene expression between the sexes and balance X and autosomal expression, two steps are believed to be required. First, an unknown mechanism is hypothesized to upregulate the X chromosome in both sexes. This mechanism balances the X to autosomal expression in males, but creates X overexpression in hermaphrodites. Therefore, to restore the balance, hermaphrodites downregulate gene expression twofold on both X chromosomes. While many studies have focused on X chromosome downregulation, the mechanism of X upregulation is not known.
Results
To gain more insight into X upregulation, we studied the effects of chromatin condensation and histone acetylation on gene expression levels in male C. elegans. We have found that the H4K16 histone acetyltransferase MYS-1/Tip60 mediates dramatic decondensation of the male X chromosome as measured by FISH. However, RNA-seq analysis revealed that MYS-1 contributes only slightly to upregulation of gene expression on the X chromosome. These results suggest that the level of chromosome decondensation does not necessarily correlate with the degree of gene expression change in vivo. Furthermore, the X chromosome is more sensitive to MYS-1-mediated decondensation than the autosomes, despite similar levels of H4K16ac on all chromosomes, as measured by ChIP-seq. H4K16ac levels weakly correlate with gene expression levels on both the X and the autosomes, but highly expressed genes on the X chromosome do not contain exceptionally high levels of H4K16ac.
Conclusion
These results indicate that H4K16ac and chromosome decondensation influence regulation of the male X chromosome; however, they do not fully account for the high levels of gene expression observed on the X chromosomes.http://deepblue.lib.umich.edu/bitstream/2027.42/134665/1/13072_2016_Article_97.pd
Origin of Immunoglobulin Isotype Switching
SummaryBackgroundFrom humans to frogs, immunoglobulin class switching introduces different effector functions to antibodies through an intrachromosomal DNA recombination process at the heavy-chain locus. Although there are two conventional antibody classes (IgM, IgW) in sharks, their heavy chains are encoded by 20 to >100 miniloci. These representatives of the earliest jawed vertebrates possess a primordial immunoglobulin gene organization where each gene cluster is autonomous and contains a few rearranging gene segments (VH-D1-D2-JH) with one constant region, μ or ω.ResultsV(D)J rearrangement always takes place within the μ cluster, but here we show that the VDJ can be expressed with constant regions from different clusters, although IgH genes are spatially distant, at >120 kb. Moreover, reciprocal exchanges take place between Igω and Igμ genes. Switching is augmented with deliberate immunization and is concomitant with somatic hypermutation activity. Because switching occurs independently of the partners' linkage position, some events involve transchromosomal recombination. The switch sites consist of direct joins between two genes in the 3′ intron flanking JH.ConclusionsOur data are consistent with a mechanism of cutting or joining of distal DNA lesions initiated by activation-induced cytidine deaminase (AID), in the absence of mammalian-type switch regions. We suggest that, in shark, with its many autonomous IgH targeted by programmed DNA breakage, factors predisposing broken DNA ends to translocate configured the earliest version of class switch recombination
Identification and Utilization of Donor and Recipient Genetic Variants to Predict Survival After HCT: Are We Ready for Primetime?
Synthesizing study-specific controls using generative models on open access datasets for harmonized multi-study analyses
Neuroimaging consortia can enhance reliability and generalizability of
findings by pooling data across studies to achieve larger sample sizes. To
adjust for site and MRI protocol effects, imaging datasets are often harmonized
based on healthy controls. When data from a control group were not collected,
statistical harmonization options are limited as patient characteristics and
acquisition-related variables may be confounded. Here, in a multi-study
neuroimaging analysis of Alzheimer's patients and controls, we tested whether
it is possible to generate synthetic control MRIs. For one case-control study,
we used a generative adversarial model for style-based harmonization to
generate site-specific controls. Downstream feature extraction, statistical
harmonization and group-level multi-study case-control and case-only analyses
were performed twice, using either true or synthetic controls. All effect sizes
using synthetic controls overlapped with those based on true study controls.
This line of work may facilitate wider inclusion of case-only studies in
multi-study consortia
Multi-robot task assignment for aerial tracking with viewpoint constraints
We address the problem of assigning a team of drones to autonomously capture a set desired shots of a dynamic target in the presence of obstacles. We present a two-stage planning pipeline that generates offline an assignment of drone to shots and locally optimizes online the viewpoint. Given desired shot parameters, the high-level planner uses a visibility heuristic to predict good times for capturing each shot and uses an Integer Linear Program to compute drone assignments. An online Model Predictive Control algorithm uses the assignments as reference to capture the shots. The algorithm is validated in hardware with a pair of drones and a remote controlled car.https://www.autonomousrobots.nl/docs/21-ray-iros.pdfAccepted manuscrip
IAT-TiMeS: Intra-Arterial Thrombectomy Transfer Metric Study in Texas
Objective: We aim to report intra-arterial thrombectomy transfer metrics for ischemic stroke patients that were transferred to hub hospitals for possible intra-arterial thrombectomy in multiple geographic regions throughout the state of Texas and to identify potential barriers and delays in the intra-arterial thrombectomy transfer process.
Method: We prospectively collected data from 8 participating Texas comprehensive stroke/thrombectomy capable centers from 7 major regions in the State of Texas. We collected baseline clinical and imaging data related to the pre-transfer evaluation, transfer metrics, and post-transfer clinical and imaging data.
Results: A total of 103 acute ischemic stroke patients suspected/confirmed to have large vessel occlusions between December 2016 to May 2019 that were transferred to hubs as possible intra-arterial thrombectomy candidates were enrolled. A total of 56 (54%) patients were sent from the spoke to the hub via ground ambulance with 47 (46%) patients traveling via air ambulance. The median spoke arrival to hub arrival time was 174 min, median spoke arrival to departure from spoke was 131 min, and median travel time was 39 min. The spoke arrival time to transfer initiation was 68 min. CT-perfusion obtained at the spoke and earlier initiation of transfer were statistically associated with shorter transfer times.
Conclusion: Transfer of intra-arterial thrombectomy patients in Texas may take over 4 h from spoke arrival to hub arrival. This time may be shortened by earlier transfer initiation and acceptance
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