433 research outputs found
Unnatural Error Correction: GPT-4 Can Almost Perfectly Handle Unnatural Scrambled Text
While Large Language Models (LLMs) have achieved remarkable performance in
many tasks, much about their inner workings remains unclear. In this study, we
present novel experimental insights into the resilience of LLMs, particularly
GPT-4, when subjected to extensive character-level permutations. To investigate
this, we first propose the Scrambled Bench, a suite designed to measure the
capacity of LLMs to handle scrambled input, in terms of both recovering
scrambled sentences and answering questions given scrambled context. The
experimental results indicate that most powerful LLMs demonstrate the
capability akin to typoglycemia, a phenomenon where humans can understand the
meaning of words even when the letters within those words are scrambled, as
long as the first and last letters remain in place. More surprisingly, we found
that only GPT-4 nearly flawlessly processes inputs with unnatural errors, even
under the extreme condition, a task that poses significant challenges for other
LLMs and often even for humans. Specifically, GPT-4 can almost perfectly
reconstruct the original sentences from scrambled ones, decreasing the edit
distance by 95%, even when all letters within each word are entirely scrambled.
It is counter-intuitive that LLMs can exhibit such resilience despite severe
disruption to input tokenization caused by scrambled text.Comment: EMNLP 2023 (with an additional analysis section in appendix
Large Language Models are Zero-Shot Reasoners
Pretrained large language models (LLMs) are widely used in many sub-fields of
natural language processing (NLP) and generally known as excellent few-shot
learners with task-specific exemplars. Notably, chain of thought (CoT)
prompting, a recent technique for eliciting complex multi-step reasoning
through step-by-step answer examples, achieved the state-of-the-art
performances in arithmetics and symbolic reasoning, difficult system-2 tasks
that do not follow the standard scaling laws for LLMs. While these successes
are often attributed to LLMs' ability for few-shot learning, we show that LLMs
are decent zero-shot reasoners by simply adding "Let's think step by step"
before each answer. Experimental results demonstrate that our Zero-shot-CoT,
using the same single prompt template, significantly outperforms zero-shot LLM
performances on diverse benchmark reasoning tasks including arithmetics
(MultiArith, GSM8K, AQUA-RAT, SVAMP), symbolic reasoning (Last Letter, Coin
Flip), and other logical reasoning tasks (Date Understanding, Tracking Shuffled
Objects), without any hand-crafted few-shot examples, e.g. increasing the
accuracy on MultiArith from 17.7% to 78.7% and GSM8K from 10.4% to 40.7% with
175B parameter InstructGPT model, as well as similar magnitudes of improvements
with another off-the-shelf large model, 540B parameter PaLM. The versatility of
this single prompt across very diverse reasoning tasks hints at untapped and
understudied fundamental zero-shot capabilities of LLMs, suggesting high-level,
multi-task broad cognitive capabilities may be extracted by simple prompting.
We hope our work not only serves as the minimal strongest zero-shot baseline
for the challenging reasoning benchmarks, but also highlights the importance of
carefully exploring and analyzing the enormous zero-shot knowledge hidden
inside LLMs before crafting finetuning datasets or few-shot exemplars.Comment: Accepted to NeurIPS2022. Our code is available at
https://github.com/kojima-takeshi188/zero_shot_co
In-cell NMR as a sensitive tool to monitor physiological condition of Escherichia coli
Sugiki, T., Yamaguchi, Y., Fujiwara, T. et al. In-cell NMR as a sensitive tool to monitor physiological condition of Escherichia coli. Sci Rep 10, 2466 (2020). https://doi.org/10.1038/s41598-020-59076-2
Reactions of 6-(N-Methylanilino)-5-(N-Phenylimino)pyrimidine-2,4 (3H, 5H)-dione with Benzyl Hydrosulfide and Benzylamine.
The expression of microRNA 574-3p as a predictor of postoperative outcome in patients with esophageal squamous cell carcinoma
Background: Despite advances in radical esophagectomies and adjuvant therapy, the postoperative prognosis in esophageal squamous cell carcinoma (ESCC) patients remains poor. The aim of this study was to identify a molecular signature to predict postoperative favorable outcomes in patients with ESCC. Methods: As a training data set, total RNA was extracted from formalin-fixed paraffin-embedded samples of surgically removed specimens from 19 ESCC patients who underwent curative esophagectomy. The expression of microRNA (miRNA) was detected using a miRNA oligo chip on which 885 genes were mounted. As a validation data set, we obtained frozen samples of surgically resected tumors from 12 independent ESCC patients and the expression of miR-574-3p was detected by quantitative real-time PCR. Results: Our microarray analysis in the training set patients identified three miRNAs (miR-574-3p, miR-106b, and miR-1303) and five miRNAs (miR-1203, miR-1909, miR-204, miR-371-3p, miR-886-3p) which were differentially expressed between the patients with (n=14) and without (n=5) postoperative tumor relapse (p<0.01 and p<0.05, respectively). Higher expression of miR-574-3p, which showed the most significant association with non-relapse (p=0.001), was associated with favorable overall survival (p=0.016). Real-time PCR experiments on the validation set patients confirmed that higher expression of miR-574-3p was associated with non-tumor relapse (p=0.029) and better overall survival (p=0.004). Conclusions: Our results suggest that the aberrant expression of the miRNAs identified in this study plays key roles in the progression of ESCC. miR-574-3p was suggested to have a tumor suppressor effect, and thus, to be a predictor of postoperative outcome in patients with ESCC
Endocytic trafficking factor VPS45 is essential for spatial regulation of lens fiber differentiation in zebrafish
In vertebrate lens, lens epithelial cells cover the anterior half of the lens fiber core. Lens epithelial cells proliferate, move posteriorly and start to differentiate into lens fiber cells at the lens equator. Although FGF signaling promotes this equatorial commencement of lens fiber differentiation, the underlying mechanism is not fully understood. Here, we show that lens epithelial cells abnormally enter lens fiber differentiation without passing through the equator in zebrafish vps45 mutants. VPS45 belongs to the Sec1/Munc18-like protein family and promotes endosome trafficking, which differentially modulates signal transduction. Ectopic lens fiber differentiation in vps45 mutants does not depend on FGF, but is mediated through activation of TGFbeta signaling and inhibition of canonical Wnt signaling. Thus, VPS45 normally suppresses lens fiber differentiation in the anterior region of lens epithelium by modulating TGFbeta and canonical Wnt signaling pathways. These data indicate a novel role of endosome trafficking to ensure equator-dependent commencement of lens fiber differentiation
Soluble Siglec-9 suppresses arthritis in a collagen-induced arthritis mouse model and inhibits M1 activation of RAW264.7 macrophages
Background: The aim of this study was to assess the effects of soluble sialic acid-binding immunoglobulin-type lectin (sSiglec)-9 on joint inflammation and destruction in a murine collagen-induced arthritis (CIA) model and in monolayer cultures of murine macrophages (RAW264.7 cells and peritoneal macrophages) and fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis.
Methods: DBA/1J mice were immunized with type II collagen. Effects of sSiglec-9 were evaluated using a physiologic arthritis score, histological analysis, serum tumor necrosis factor (TNF)-α concentration, and the proportion of forkhead box P3 (Foxp3)-positive regulatory T (Treg) cells. In vivo biofluorescence imaging was used to assess the distribution of sSiglec-9. Levels of M1 (TNF-α, interleukin [IL]-6, and inducible nitric oxide synthase) and M2 (CD206, Arginase-1, and IL-10) macrophage markers and phosphorylation of intracellular signaling molecules were examined in macrophages, and levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were examined in FLS.
Results: sSiglec-9 significantly suppressed the clinical and histological incidence and severity of arthritis. The proportion of Foxp3-positive Treg cells significantly improved and serum TNF-α concentration decreased in vivo. Although sSiglec-9 reduced the expression of M1 markers in macrophages, it did not affect the expression of M2 markers and MMPs in FLS. Nuclear factor (NF)-kB p65 phosphorylation was attenuated by sSiglec-9, and chemical blockade of the NF-kB pathway reduced M1 marker expression in RAW264.7 cells.
Conclusions: In this study, we have demonstrated the therapeutic effects of sSiglec-9 in a murine CIA model. The mechanism underlying these effects involves the suppression of M1 proinflammatory macrophages by inhibiting the NF-kB pathway. sSiglec-9 may provide a novel therapeutic option for patients with rheumatoid arthritis refractory to currently available drugs
The BH3-Only SNARE BNip1 Mediates Photoreceptor Apoptosis in Response to Vesicular Fusion Defects
SummaryIntracellular vesicular transport is important for photoreceptor function and maintenance. However, the mechanism underlying photoreceptor degeneration in response to vesicular transport defects is unknown. Here, we report that photoreceptors undergo apoptosis in a zebrafish β-soluble N-ethylmaleimide-sensitive factor attachment protein (β-SNAP) mutant. β-SNAP cooperates with N-ethylmaleimide-sensitive factor to recycle the SNAP receptor (SNARE), a key component of the membrane fusion machinery, by disassembling the cis-SNARE complex generated in the vesicular fusion process. We found that photoreceptor apoptosis in the β-SNAP mutant was dependent on the BH3-only protein BNip1. BNip1 functions as a component of the syntaxin-18 SNARE complex and regulates retrograde transport from the Golgi to the endoplasmic reticulum. Failure to disassemble the syntaxin-18 cis-SNARE complex caused BNip1-dependent apoptosis. These data suggest that the syntaxin-18 cis-SNARE complex functions as an alarm factor that monitors vesicular fusion competence and that BNip1 transforms vesicular fusion defects into photoreceptor apoptosis
BUROSUMAB IN TUMOR-INDUCED OSTEOMALACIA
Patients with tumor-induced osteomalacia (TIO), an acquired paraneoplastic condition characterized by osteomalacia due to hypophosphatemia, exhibit a similar clinical picture to those with X-linked hypophosphatemic rickets/osteomalacia (XLH). The human monoclonal anti-fibroblast growth factor 23 (FGF23) antibody burosumab (KRN23) increases serum phosphate and improves bone turnover, fracture healing, pain, and physical function in XLH patients by inhibiting circulating FGF23; thus, burosumab is expected to be an effective treatment for TIO. We report here an interim analysis of a multicenter, open-label, intraindividual dose-adjustment study of burosumab (0.3 to 2.0 mg/kg every 4 weeks) in Japanese and Korean TIO patients. The primary endpoint was the fasting serum phosphate level at each visit. Key secondary endpoints were changes over time in bone biomarkers, pharmacodynamic markers, bone histomorphometric parameters, motor function, and patient-reported outcomes. Safety was assessed based on treatment-emergent adverse events (TEAEs). Thirteen patients received burosumab treatment, of whom 4 underwent bone biopsy. The mean dose after week 112 was approximately 1.0 mg/kg. After the first burosumab administration, mean serum phosphate levels increased and remained above the lower limit of normal and in the normal range from weeks 14 to 112. Bone biomarkers initially increased, reaching maximum values at week 16 or 24, and then gradually decreased. After burosumab treatment, patients were able to walk further (evaluated by the 6-minute walk test), reported decreased pain levels, and showed a tendency toward healing of baseline fractures and pseudofractures. Two patients discontinued, one each due to disease progression and consent withdrawal. Burosumab was generally well tolerated, with no treatment-related TEAEs of grade ≥3 and no treatment-related serious AEs. In conclusion, the interim results of this first study of burosumab to treat TIO patients indicate that this drug has the potential to provide clinical benefit for patients with unresectable tumors. The full study results are eagerly anticipated
- …