242 research outputs found

    The CoT Collection: Improving Zero-shot and Few-shot Learning of Language Models via Chain-of-Thought Fine-Tuning

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    Language models (LMs) with less than 100B parameters are known to perform poorly on chain-of-thought (CoT) reasoning in contrast to large LMs when solving unseen tasks. In this work, we aim to equip smaller LMs with the step-by-step reasoning capability by instruction tuning with CoT rationales. In order to achieve this goal, we first introduce a new instruction-tuning dataset called the CoT Collection, which augments the existing Flan Collection (including only 9 CoT tasks) with additional 1.84 million rationales across 1,060 tasks. We show that CoT fine-tuning Flan-T5 (3B & 11B) with CoT Collection enables smaller LMs to have better CoT capabilities on unseen tasks. On the BIG-Bench-Hard (BBH) benchmark, we report an average improvement of +4.34% (Flan-T5 3B) and +2.60% (Flan-T5 11B), in terms of zero-shot task accuracy. Furthermore, we show that instruction tuning with CoT Collection allows LMs to possess stronger few-shot learning capabilities on 4 domain-specific tasks, resulting in an improvement of +2.24% (Flan-T5 3B) and +2.37% (Flan-T5 11B), even outperforming ChatGPT utilizing demonstrations until the max length by a +13.98% margin. Our code, the CoT Collection data, and model checkpoints are publicly available.Comment: EMNLP 2023 (Main Conference

    Assessment of Bone Quality using Finite Element Analysis Based upon Micro-CT Images

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    BACKGROUND: To evaluate the feasibility of a micro-image based finite element model to determine the efficacy of sequential treatments on the bone quality in a rat osteoporosis model. METHODS: Rat osteoporosis and treated osteoporosis models were established with the bone loss, restore and maintain concept. Thirty Sprague-Dawley rats were used in this study. A sham operation or ovariectomy was performed at 20 weeks after birth, which was followed by the respective sequential trials as follows: (1) sham-operation only, (2) ovariectomy only, (3) ovariectomized rats with parathyroid hormone maintenance, (4) ovariectomized rats treated with PTH for 5 weeks and then withdrawal, (5) ovariectomized rats treated with PTH for 5 weeks and then with 17 beta-estradiol, and (6) ovariectomized rats treated with parathyroid hormone for 5 weeks and then treated with zoledronate. The histomorphometry indices were determined using the micro-images from a micro-computed tomogram. Finite element analysis was carried out to determine the mechanical properties (Stiffness and Young's modulus) of the vertebra bodies. The differences in properties between the groups were compared using ANOVA and a Bonferroni's multiple group comparison procedure. RESULTS: The histomorphometry and mechanical properties were significantly better in groups (3) and (6) than in the groups (1) and (2) (p < 0.05). The stiffness (sigma(s)) and Young's modulus (E) was highest in group (3) following by group (6). CONCLUSIONS: Finite element analysis based on micro-images provides a useful tool that reflects the changes in micro-structural and mechanical properties of a rat vertebral body with the bone loss, restore and maintain concept.ope

    Comparison between Occlusal Errors of Single Posterior Crowns Adjusted Using Patient Specific Motion or Conventional Methods

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    Recently, digital technology has been used in dentistry to enhance accuracy and to reduce operative time. Due to advances in digital technology, the integration of individual mandibular motion into the mapping of the occlusal surface is being attempted. The Patient Specific Motion (PSM) is one such method. However, it is not clear whether the occlusal design that is adjusted using PSM could clinically show reduced occlusal error compared to conventional methods based on static occlusion. In this clinical comparative study including fifteen patients with a single posterior zirconia crown treatment, the occlusal surface after a clinical adjustment was compared to no adjustment (NA; design based on static occlusion), PSM (adjusted using PSM), and adjustment using a semi-adjustable articulator (SA) for the assessment of occlusal error. The root mean square (RMS; mu m), average deviation value (+/- AVG; mu m), and proportion inside the tolerance (in Tol; %) were calculated using the entire, subdivided occlusal surface and the out of tolerance area. Using a one-way ANOVA, the RMS and +AVG from the out of tolerance area showed a statistical difference between PSM (202.3 +/- 39.8 for RMS, 173.1 +/- 31.3 for +AVG) and NA (257.0 +/- 73.9 for RMS, 210.9 +/- 48.6 for +AVG). For the entire and subdivided occlusal surfaces, there were no significant differences. In the color-coded map analysis, PSM demonstrated a reduced occlusal error compared to NA. In conclusion, adjustment occlusal design using PSM is a simple and effective method for reducing occlusal errors that are difficult to identify in a current computer-aided design (CAD) workflow with static occlusion.11Nsciescopu

    Effects of a Novel Nitroxyl Donor in Acute Heart Failure The STAND-UP AHF Study

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    Objectives: The primary objective was to identify well-tolerated doses of cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events. Background: Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects. Bristol-Myers Squibb-986231 (cimlanod) is an HNO donor being developed for acute heart failure (AHF). Methods: This was a phase IIb, double-blind, randomized, placebo-controlled trial of 48-h treatment with cimlanod compared with placebo in patients with left ventricular ejection fraction ≤40% hospitalized for AHF. In part I, patients were randomized in a 1:1 ratio to escalating doses of cimlanod or matching placebo. In part II, patients were randomized in a 1:1:1 ratio to either of the 2 highest tolerated doses of cimlanod from part I or placebo. The primary endpoint was the rate of clinically relevant hypotension (systolic blood pressure &lt;90 mm Hg or patients became symptomatic). Results: In part I (n = 100), clinically relevant hypotension was more common with cimlanod than placebo (20% vs. 8%; relative risk [RR]: 2.45; 95% confidence interval [CI]: 0.83 to 14.53). In part II (n = 222), the incidence of clinically relevant hypotension was 18% for placebo, 21% for cimlanod 6 μg/kg/min (RR: 1.15; 95% CI: 0.58 to 2.43), and 35% for cimlanod 12 μg/kg/min (RR: 1.9; 95% CI: 1.04 to 3.59). N-terminal pro–B-type natriuretic peptide and bilirubin decreased during infusion of cimlanod treatment compared with placebo, but these differences did not persist after treatment discontinuation. Conclusions: Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period. (Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure [STANDUP AHF]; NCT03016325

    Toward a molecular pathogenic pathway for Yersinia pestis YopM

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    YopM is one of the six “effector Yops” of the human-pathogenic Yersinia, but its mechanism has not been defined. After delivery to J774A.1 monocyte-like cells, YopM can rapidly bind and activate the serine/threonine kinases RSK1 and PRK2. However, in infected mice, effects of Y. pestis YopM have been seen only after 24–48 h post-infection (p.i.). To identify potential direct effects of YopM in-vivo we tested for effects of YopM at 1 h and 16–18 h p.i. in mice infected systemically with 106 bacteria. At 16 h p.i., there was a robust host response to both parent and ΔyopM-1 Y. pestis KIM5. Compared to cells from non-infected mice, CD11b+ cells from spleens of infected mice produced more than 100-fold greater IFNγ. In the corresponding sera there were more than 100-fold greater amounts of IFNγ, G-CSF, and CXCL9, as well as more than 10-fold greater amounts of IL-6, CXCL10, and CXCL1. The only YopM-related differences were slightly lower CXCL10 and IL-6 in sera from mice infected 16 h with parent compared to ΔyopM-1 Y. pestis. Microarray analysis of the CD11b+ cells did not identify consistent transcriptional differences of ≥4-fold at 18 h p.i. However, at 1 h p.i. mRNA for early growth response transcription factor 1 (Egr1) was decreased when YopM was present. Bone marrow-derived macrophages infected for 1 h also expressed lower Egr1 message when YopM was present. Infected J774A.1 cells showed greater expression of Egr1 at 1 h p.i. when YopM was present, but this pattern reversed at 3 h. At 6 h p.i., Cxcl10 mRNA was lower in parent-strain infected cells. We conclude that decreased Egr1 expression is a very early transcriptional effect of YopM and speculate that a pathway may exist from RSK1 through Egr1. These studies revealed novel early transcriptional effects of YopM but point to a time after 18 h of infection when critical transitional events lead to later major effects on cytokine gene transcription

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
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