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We give the first provably efficient algorithms for learning neural networks with distribution shift. We work in the Testable Learning with Distribution Shift framework (TDS learning) of Klivans et al. (2024), where the learner receives labeled examples from a training distribution and unlabeled examples from a test distribution and must either output a hypothesis with low test error or reject if distribution shift is detected. No assumptions are made on the test distribution. All prior work in TDS learning focuses on classification, while here we must handle the setting of nonconvex regression. Our results apply to real-valued networks with arbitrary Lipschitz activations and work whenever the training distribution has strictly sub-exponential tails. For training distributions that are bounded and hypercontractive, we give a fully polynomial-time algorithm for TDS learning one hidden-layer networks with sigmoid activations. We achieve this by importing classical kernel methods into the TDS framework using data-dependent feature maps and a type of kernel matrix that couples samples from both train and test distributions. 

Abstract Human induced pluripotent stem cell-derived (iPSC) neural cultures offer clinically relevant models of human diseases, including Amyotrophic Lateral Sclerosis, Alzheimer’s, and Autism Spectrum Disorder. In situ characterization of the spatial-temporal evolution of cell state in 3D culture and subsequent 2D dissociated culture models based on protein expression levels and localizations is essential to understanding neural cell differentiation, disease state phenotypes, and sample-to-sample variability. Here, we apply PR obe-based I maging for S equential M ultiplexing (PRISM) to facilitate multiplexed imaging with facile, rapid exchange of imaging probes to analyze iPSC-derived cortical and motor neuron cultures that are relevant to psychiatric and neurodegenerative disease models, using over ten protein targets. Our approach permits analysis of cell differentiation, cell composition, and functional marker expression in complex stem-cell derived neural cultures. Furthermore, our approach is amenable to automation, offering in principle the ability to scale-up to dozens of protein targets and samples. 

Background Hypertension drives myocardial remodeling, leading to changes in structure, composition and mechanical behavior, including residual stress, which are linked to heart disease progression in a gender-specific manner. Emerging therapies are also targeting constituent-specific pathological features. All previous studies, however, have characterized remodeling in the intact tissue, rather than isolated tissue constituents, and did not include sex as a biological variable. Objective In this study we first identified the contribution of collagen fiber network and myocytes to the myocardial residual stress/strain in Dahl-Salt sensitive rats fed with high fat diet. Then, we quantified the effect of hypertension on the remodeling of the left ventricle (LV), as well as the existence of sex-specific remodeling features. Methods We performed mechanical tests (opening angle, ring-test) and histological analysis on isolated constituents and intact tissue of the LV. Based on the measurements from the tests, we performed a stress analysis to evaluate the residual stress distribution. Statistical analysis was performed to identify the effects of constituent isolation, elevated blood pressure, and sex of the animal on the experimental measurements and modeling results. Results Hypertension leads to reduced residual stress/strain in the intact tissue, isolated collagen fibers, and isolated myocytes in male and female rats. Collagen remains the largest contributor to myocardial residual stress in both normotensive and hypertensive animals. We identified sex-differences in both hypertensive and normotensive animals. Conclusions We observed both constituent- and sex-specific remodeling features in the LV of an animal model of hypertension. 

We report on one of the highest sensitivity surveys for molecular lines in the frequency range 6.0 to 7.4 GHz conducted to date. The observations were done with the 305m Arecibo Telescope toward a sample of twelve intermediate/high-mass star forming regions. We searched for a large number of transitions of different molecules, including CH3OH and OH. The low RMS noise of our data (~5 mJy for most sources and transitions) allowed detection of spectral features that have not been seen in previous lower sensitivity observations of the sources, such as detection of excited OH and 6.7 GHz CH3OH absorption. A review of 6.7 GHz CH3OH detections indicates an association between absorption and radio continuum sources in high-mass star forming regions, although selection biases in targeted projects and low sensitivity of blind surveys imply incompleteness. Absorption of excited OH transitions was also detected toward three sources. In particular, we confirm a broad 6.035 GHz OH absorption feature in G34.26+0.15 characterized by an asymmetric blue-shifted wing indicative of expansion, perhaps a large scale outflow in this HII region. 

Agrobacterium-mediated T-DNA integration into the plant genomes is random, which often causes variable transgene expression and insertional mutagenesis. Because T-DNA preferentially integrates into double-strand DNA breaks, we adapted a CRISPR/Cas9 system to demonstrate that targeted T-DNA integration can be achieved in the rice genome. Using a standard Agrobacterium binary vector, we constructed a T-DNA that contains a CRISPR/Cas9 system using SpCas9 and a gRNA targeting the exon of the rice AP2 domain-containing protein gene Os01g04020. The T-DNA also carried a red fluorescent protein and a hygromycin resistance (hptII) gene. One version of the vector had hptII expression driven by an OsAct2 promoter. In an effort to detect targeted T-DNA insertion events, we built another T-DNA with a promoterless hptII gene adjacent to the T-DNA right border such that integration of T-DNA into the targeted exon sequence in-frame with the hptII gene would allow hptII expression. Our results showed that these constructs could produce targeted T-DNA insertions with frequencies ranging between 4 and 5.3% of transgenic callus events, in addition to generating a high frequency (50−80%) of targeted indel mutations. Sequencing analyses showed that four out of five sequenced T-DNA/gDNA junctions carry a single copy of full-length T-DNA at the target site. Our results indicate that Agrobacterium-mediated transformation combined with a CRISPR/Cas9 system can efficiently generate targeted T-DNA insertions. 

The prevalence of disease-driven mass mortality events is increasing, but our understanding of spatial variation in their magnitude, timing and triggers are often poorly resolved. Here, we use a novel range-wide dataset comprised 48 810 surveys to quantify how sea star wasting disease affected Pycnopodia helianthoides , the sunflower sea star, across its range from Baja California, Mexico to the Aleutian Islands, USA. We found that the outbreak occurred more rapidly, killed a greater percentage of the population and left fewer survivors in the southern half of the species's range. Pycnopodia now appears to be functionally extinct (greater than 99.2% declines) from Baja California, Mexico to Cape Flattery, Washington, USA and exhibited severe declines (greater than 87.8%) from the Salish Sea to the Gulf of Alaska. The importance of temperature in predicting Pycnopodia distribution rose more than fourfold after the outbreak, suggesting latitudinal variation in outbreak severity may stem from an interaction between disease severity and warmer waters. We found no evidence of population recovery in the years since the outbreak. Natural recovery in the southern half of the range is unlikely over the short term. Thus, assisted recovery will probably be required to restore the functional role of this predator on ecologically relevant time scales. 

Abstract Despite the f₀(980) hadron having been discovered half a century ago, the question about its quark content has not been settled: it might be an ordinary quark-antiquark ($${{\rm{q}}}\overline{{{\rm{q}}}}$$ $q\overline{q}$) meson, a tetraquark ($${{\rm{q}}}\overline{{{\rm{q}}}}{{\rm{q}}}\overline{{{\rm{q}}}}$$ $q\overline{q}q\overline{q}$) exotic state, a kaon-antikaon ($${{\rm{K}}}\overline{{{\rm{K}}}}$$ $K\overline{K}$) molecule, or a quark-antiquark-gluon ($${{\rm{q}}}\overline{{{\rm{q}}}}{{\rm{g}}}$$ $q\overline{q}g$) hybrid. This paper reports strong evidence that the f₀(980) state is an ordinary$${{\rm{q}}}\overline{{{\rm{q}}}}$$ $q\overline{q}$meson, inferred from the scaling of elliptic anisotropies (v₂) with the number of constituent quarks (n_q), as empirically established using conventional hadrons in relativistic heavy ion collisions. The f₀(980) state is reconstructed via its dominant decay channel f₀(980) →π⁺π⁻, in proton-lead collisions recorded by the CMS experiment at the LHC, and itsv₂is measured as a function of transverse momentum (p_T). It is found that then_q= 2 ($${{\rm{q}}}\overline{{{\rm{q}}}}$$ $q\overline{q}$state) hypothesis is favored overn_q= 4 ($${{\rm{q}}}\overline{{{\rm{q}}}}{{\rm{q}}}\overline{{{\rm{q}}}}$$ $q\overline{q}q\overline{q}$or$${{\rm{K}}}\overline{{{\rm{K}}}}$$ $K\overline{K}$states) by 7.7, 6.3, or 3.1 standard deviations in thep_T< 10, 8, or 6 GeV/cranges, respectively, and overn_q= 3 ($${{\rm{q}}}\overline{{{\rm{q}}}}{{\rm{g}}}$$ $q\overline{q}g$hybrid state) by 3.5 standard deviations in thep_T< 8 GeV/crange. This result represents the first determination of the quark content of the f₀(980) state, made possible by using a novel approach, and paves the way for similar studies of other exotic hadron candidates.