Enabling Calibration In The Zero-Shot Inference of Large Vision-Language Models

Calibration of deep learning models is crucial to their trustworthiness and safe usage, and as such, has been extensively studied in supervised classification models, with methods crafted to decrease miscalibration. However, there has yet to be a comprehensive study of the calibration of vision-language models that are used for zero-shot inference, like CLIP. We measure calibration across relevant variables like prompt, dataset, and architecture, and find that zero-shot inference with CLIP is miscalibrated. Furthermore, we propose a modified version of temperature scaling that is aligned with the common use cases of CLIP as a zero-shot inference model, and show that a single learned temperature generalizes for each specific CLIP model (defined by a chosen pre-training dataset and architecture) across inference dataset and prompt choice

Measuring trust in vaccination: A systematic review.

Vaccine acceptance depends on public trust and confidence in the safety and efficacy of vaccines and immunization, the health system, healthcare professionals and the wider vaccine research community. This systematic review analyses the current breadth and depth of vaccine research literature that explicitly refers to the concept of trust within their stated aims or research questions. After duplicates were removed, 19,643 articles were screened by title and abstract. Of these 2,779 were screened by full text, 35 of which were included in the final analysis. These studies examined a range of trust relationships as they pertain to vaccination, including trust in healthcare professionals, the health system, the government, and friends and family members. Three studies examined generalized trust. Findings indicated that trust is often referred to implicitly (19/35), rather than explicitly examined in the context of a formal definition or discussion of the existing literature on trust in a health context. Within the quantitative research analysed, trust was commonly measured with a single-item measure (9/25). Only two studies used validated multi-item measures of trust. Three studies examined changes in trust, either following an intervention or over the course of a pandemic. The findings of this review indicate a disconnect between the current vaccine hesitancy research and the wider health-related trust literature, a dearth in research on trust in low and middle-income settings, a need for studies on how trust levels change over time and investigations on how resilience to trust-eroding information can be built into a trustworthy health system

Omnidirectional Transfer for Quasilinear Lifelong Learning

In biological learning, data are used to improve performance not only on the current task, but also on previously encountered and as yet unencountered tasks. In contrast, classical machine learning starts from a blank slate, or tabula rasa, using data only for the single task at hand. While typical transfer learning algorithms can improve performance on future tasks, their performance on prior tasks degrades upon learning new tasks (called catastrophic forgetting). Many recent approaches for continual or lifelong learning have attempted to maintain performance given new tasks. But striving to avoid forgetting sets the goal unnecessarily low: the goal of lifelong learning, whether biological or artificial, should be to improve performance on all tasks (including past and future) with any new data. We propose omnidirectional transfer learning algorithms, which includes two special cases of interest: decision forests and deep networks. Our key insight is the development of the omni-voter layer, which ensembles representations learned independently on all tasks to jointly decide how to proceed on any given new data point, thereby improving performance on both past and future tasks. Our algorithms demonstrate omnidirectional transfer in a variety of simulated and real data scenarios, including tabular data, image data, spoken data, and adversarial tasks. Moreover, they do so with quasilinear space and time complexity

Alternative splicing and bioinformatic analysis of human U12-type introns

U12-type introns exist, albeit rarely, in a variety of multicellular organisms. Splicing of U12 intron-containing precursor mRNAs takes place in the U12-type spliceosome that is distinct from the major U2-type spliceosome. Due to incompatibility of these two spliceosomes, alternative splicing involving a U12-type intron may give rise to a relatively complicated impact on gene expression. We studied alternative U12-type intron splicing in an attempt to gain more mechanistic insights. First, we characterized mutually exclusive exon selection of the human JNK2 gene, which involves an unusual intron possessing the U12-type 5′ splice site and the U2-type 3′ splice site. We demonstrated that the long and evolutionary conserved polypyrimidine tract of this hybrid intron provides important signals for inclusion of its downstream alternative exon. In addition, we examined the effects of single nucleotide polymorphisms in the human WDFY1 U12-type intron on pre-mRNA splicing. These results provide mechanistic implications on splice-site selection of U12-type intron splicing. We finally discuss the potential effects of splicing of a U12-type intron with genetic defects or within a set of genes encoding RNA processing factors on global gene expression

The Search for Gravitational Waves

Experiments aimed at searching for gravitational waves from astrophysical sources have been under development for the last 40 years, but only now are sensitivities reaching the level where there is a real possibility of detections being made within the next five years. In this article a history of detector development will be followed by a description of current detectors such as LIGO, VIRGO, GEO 600, TAMA 300, Nautilus and Auriga. Preliminary results from these detectors will be discussed and related to predicted detection rates for some types of sources. Experimental challenges for detector design are introduced and discussed in the context of detector developments for the future.Comment: 21 pages, 7 figures, accepted J. Phys. B: At. Mol. Opt. Phy

Comprehensive splice-site analysis using comparative genomics

We have collected over half a million splice sites from five species—Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana—and classified them into four subtypes: U2-type GT–AG and GC–AG and U12-type GT–AG and AT–AC. We have also found new examples of rare splice-site categories, such as U12-type introns without canonical borders, and U2-dependent AT–AC introns. The splice-site sequences and several tools to explore them are available on a public website (SpliceRack). For the U12-type introns, we find several features conserved across species, as well as a clustering of these introns on genes. Using the information content of the splice-site motifs, and the phylogenetic distance between them, we identify: (i) a higher degree of conservation in the exonic portion of the U2-type splice sites in more complex organisms; (ii) conservation of exonic nucleotides for U12-type splice sites; (iii) divergent evolution of C.elegans 3′ splice sites (3′ss) and (iv) distinct evolutionary histories of 5′ and 3′ss. Our study proves that the identification of broad patterns in naturally-occurring splice sites, through the analysis of genomic datasets, provides mechanistic and evolutionary insights into pre-mRNA splicing

A conserved myotubularin-related phosphatase regulates autophagy by maintaining autophagic flux

Macroautophagy (autophagy) targets cytoplasmic cargoes to the lysosome for degradation. Like all vesicle trafficking, autophagy relies on phosphoinositide identity, concentration, and localization to execute multiple steps in this catabolic process. Here, we screen for phosphoinositide phosphatases that influence autophagy in Drosophila and identify CG3530. CG3530 is homologous to the human MTMR6 subfamily of myotubularin-related 3-phosphatases, and therefore, we named it dMtmr6. dMtmr6, which is required for development and viability in Drosophila, functions as a regulator of autophagic flux in multiple Drosophila cell types. The MTMR6 family member MTMR8 has a similar function in autophagy of higher animal cells. Decreased dMtmr6 and MTMR8 function results in autophagic vesicle accumulation and influences endolysosomal homeostasis

The significant other: splicing by the minor spliceosome

Peer reviewe

Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals

<p>Abstract</p> <p>Background</p> <p>Metformin protection against cancer risk in Orientals is uncertain. We examined the possible metformin effect on total, esophageal, gastric, colorectal (CRC), hepatocellular (HCC) and pancreatic cancers in a Taiwanese cohort.</p> <p>Methods</p> <p>A representative sample of 800,000 was drawn from the Taiwanese National Health Insurance data of 2000. A cohort of 480,984 participants 20 years or older, diabetes-cancer-free on 1st January 2000 was formed and categorized as four groups by DM and metformin usage status. Eligible incident cancer events had to occur one year after the index date until the end of 2007. The Cox proportional-hazards model evaluated relative risk of cancer for treated DM patients with or without metformin. The covariates included age, gender, other oral anti-hyperglycemic medication, Charlson comorbidity index (CCI) score and metformin exposure dosage and duration.</p> <p>Results</p> <p>With diabetes but no anti-hyperglycemic medication, cancer incidence density increased at least 2-fold for total, CRC and HCC. On metformin, total, CRC and HCC incidences decreased to near non-diabetic levels but to varying degrees depending on gender and cancer type (CRC in women, liver in men). Adjustment for other oral anti-hyperglycemic agents usage and CCI made the benefit of metformin more evident [hazard ratios (95% confidence intervals): total 0.12 (0.08-0.19), CRC 0.36 (0.13-0.98), liver 0.06 (0.02-0.16), pancreas 0.15 (0.03-0.79)]. There was a significant gender interaction with metformin in CRC which favored women. Metformin dosage for a significant decrease in cancer incidence was ≤500 mg/day.</p> <p>Conclusions</p> <p>Metformin can reduce the incidences of several gastroenterological cancers in treated diabetes.</p

Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival

<p>Abstract</p> <p>Background</p> <p>The JAK2^V617Fmutation plays a major role in the pathogenesis of myeloproliferative neoplasms and is found in the vast majority of patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia or from primary myelofibrosis. The V617F mutation is thought to provide hematopoietic stem cells and myeloid progenitors with a survival and proliferation advantage. It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL. In this study, we have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1.</p> <p>Methods</p> <p>Pharmacological inhibition of JAK2/STAT5 signaling in JAK2^V617Fmutant SET-2 and MB-02 cells was used to study effects on signaling, cell proliferation and apoptosis by Western blot analysis, WST-1 proliferation assays and flow cytometry. Cells were transfected with siRNA oligos to deplete candidate pro- and anti-apoptotic proteins. Co-immunoprecipitation assays were performed to assess the impact of JAK2 inhibition on complexes of pro- and anti-apoptotic proteins.</p> <p>Results</p> <p>Treatment of JAK2^V617Fmutant cell lines with a JAK2 inhibitor was found to trigger Bim activation. Furthermore, Bim depletion by RNAi suppressed JAK2 inhibitor-induced cell death. Bim activation following JAK2 inhibition led to enhanced sequestration of Mcl-1, besides Bcl-xL. Importantly, Mcl-1 depletion by RNAi was sufficient to compromise JAK2^V617Fmutant cell viability and sensitized the cells to JAK2 inhibition.</p> <p>Conclusions</p> <p>We conclude that Bim and Mcl-1 have key opposing roles in regulating JAK2^V617Fcell survival and propose that inactivation of aberrant JAK2 signaling leads to changes in Bim complexes that trigger cell death. Thus, further preclinical evaluation of combinations of JAK2 inhibitors with Bcl-2 family antagonists that also tackle Mcl-1, besides Bcl-xL, is warranted to assess the therapeutic potential for the treatment of chronic myeloproliferative neoplasms.</p