gebhart/patrepeval huggingface dataset:
Improving Data-Efficiency and Robustness of Medical Imaging Segmentation Using Inpainting-Based Self-Supervised Learning (2023)

We systematically evaluate the training methodology and efficacy of two inpainting-based pretext tasks of context prediction and context restoration for medical image segmentation using self-supervised learning (SSL). Multiple versions of self-supervised U-Net models were trained to segment MRI and CT datasets, each using a different combination of design choices and pretext tasks to determine the effect of these design choices on segmentation performance. The optimal design choices were used to train SSL models that were then compared with baseline supervised models for computing clinically-relevant metrics in label-limited scenarios. We observed that SSL pretraining with context restoration using 32 × 32 patches and Poission-disc sampling, transferring only the pretrained encoder weights, and fine-tuning immediately with an initial learning rate of 1 × 10-3 provided the most benefit over supervised learning for MRI and CT tissue segmentation accuracy (<i>p</i> < 0.001). For both datasets and most label-limited scenarios, scaling the size of unlabeled pretraining data resulted in improved segmentation performance. SSL models pretrained with this amount of data outperformed baseline supervised models in the computation of clinically-relevant metrics, especially when the performance of supervised learning was low. Our results demonstrate that SSL pretraining using inpainting-based pretext tasks can help increase the robustness of models in label-limited scenarios and reduce worst-case errors that occur with supervised learning.
IMPROVEMENT IN PULMONARY FUNCTION IMMEDIATELY AFTER SURGICAL REDUCTION OF CONGENITAL DIAPHRAGMATIC HERNIA IN LAMBS (1998)

S547 INTRODUCTION: Modern trends are towards delayed surgical reduction of congenital diaphragmatic hernia (CDH) [1]. In our experience, we have found that infants with CDH are "easier" to ventilate postoperatively, provided that air is left in the ipsilateral chest cavity in order to protect the lungs from overdistension [2]. We hypothesized that "ease" of ventilation is associated with post-surgical improvement in pulmonary mechanics. METHODS: Very severe CDH was surgically induced in utero at 90 days of gestation in 31 lambs [3]. At birth (134-142 days of gestation), functional residual capacity (FRC) and pulmonary mechanics (PeDS-Lab, Hatfield, PA) were measured in these preterm lambs with (n = 24) and without (n = 7) early surgical reduction, and in 8 non-CDH controls over the same period of time. All animals were tracheotomized and gas mechanically ventilated at FIO2 = 1.0. Management excluded aspiration and chest drains. Statistical analyses of data were performed using Student's t test or one factor Anova followed by Dunnett's post hoc test, and acceptance at p < 0.05. RESULTS: Born with similar poor pulmonary function (compliance at 0.07 +/- 0.01 (SE) mL/cmH2 O/kg), after 30 min of life CDH animals with early surgical reduction demonstrated significantly greater improvement in lung volume, pulmonary mechanics, and oxygenation than those without reduction: FRC 4.7 +/- 1.5 vs 3.1 +/- 1.8 mL/kg, compliance 0.11 +/- 0.01 vs 0.08 +/- 0.01 mL/cmH2 O/kg, minute ventilation 219 +/- 16 vs 163 +/- 21 mL/min and pO2 128 +/- 29 vs 67 +/- 9 torr. Over the same period of time, compliance in preterm controls varied from 0.22 +/- 0.05 to 0.29 +/- 0.05 mL/cmH2 O/kg, while other respiratory values remained stable. CONCLUSION: Based on the mechanics of breathing in these lambs, we speculate that neonates with CDH would benefit from early surgical repair due to improvement in pulmonary function, provided extra care is taken to prevent pulmonary overdistension. Further experiments are needed to evaluate long term issues and treatments.
Recent advances in the discovery and synthesis of neuraminidase inhibitors (2005)

AbstractThe influenza virus neuraminidase (NA) is important in the pathogenesis of infection and, thus, is an attractive target for agents used in the treatment and prophylaxis of influenza. Two drugs discovered from the structure-based drug design of neuraminidase inhibitors, zanamivir and oseltamivir phosphate, were approved by the FDA in 1999. Both drugs are effective in the control of influenza infections in humans. As pandemic is a worldwide outbreak, there is still continuous interest in this disease, and 15 patents on neuraminidase inhibitors have appeared in the literature since the last review in November 2001. This article updates the patent literature since then. As syntheses were not given in the previous review article, the details of the synthesis of both drugs, zanamivir and oseltamivir phosphate, and of other potent inhibitors, (-)-(1S,2S,3R,4R)-3-[(1S)-1-(acetylamino)-2-ethylbutyl]-4-{[amino(imino)methyl]amino}-2-hydroxycyclopentanecarboxylic acid (peramivir, BCX-1812 or RWJ-270201), (-)-(2R,4S,5R)-5-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-4-[(1Z)-prop-1-enyl]pyrrolidine-2-carboxylic acid (ABT-675) and Biota's polymeric compounds, are also revealed in this article.Keywords:: ABT-675BCX-1812neuraminidase inhibitoroseltamivirzanamivir
Unique metabolites protect earthworms against plant polyphenols (2015)

All higher plants produce polyphenols, for defence against above-ground herbivory. These polyphenols also influence the soil micro- and macro-fauna that break down plant leaf litter. Polyphenols therefore indirectly affect the fluxes of soil nutrients and, ultimately, carbon turnover and ecosystem functioning in soils. It is unknown how earthworms, the major component of animal biomass in many soils, cope with high-polyphenol diets. Here, we show that earthworms possess a class of unique surface-active metabolites in their gut, which we term 'drilodefensins'. These compounds counteract the inhibitory effects of polyphenols on earthworm gut enzymes, and high-polyphenol diets increase drilodefensin concentrations in both laboratory and field populations. This shows that drilodefensins protect earthworms from the harmful effects of ingested polyphenols. We have identified the key mechanism for adaptation to a dietary challenge in an animal group that has a major role in organic matter recycling in soils worldwide.
Catalyst-Free and Scalable Process for Synthesis of Novel MAP4K4 Inhibitor DMX-5804 and Its Glyco-Conjugates (2021)

DMX-5804 is a potent and selective mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) inhibitor, which is currently under evaluation for the treatment of myocardial infarction. Here, we report the process development of scalable and practical synthesis of DMX-5804. Process optimization resulted in the following: (1) removal of transition metals from the process and reduced duration of reactions, (2) a streamlined process with significantly improved yields using low-cost raw materials, (3) importantly, microwave-assisted reactions were removed, (4) column purification avoided throughout the process, and (5) crystallized products showed over 95% purity in each step.
Supramolecular Modification of a Metal-Organic Framework Increases Flexibility and Switchability: Experimental Insights into Structural Deformation of ZIF-8 (2022)

Use of chemical modulators during the synthesis of a coordination framework is an important strategy to affect and tune properties of porous materials. Herein, we introduce an approach to understanding structural modulation and deformation of soft, porous crystals in the context of gas adsorption by using atomic force microscopy (AFM) nanoindentation and physisorption analysis. Modified nanocrystals of the prototypical zeolitic-imidazolate framework-8 (ZIF-8) were generated in triethylamine (Et3N) via an in-situ supramolecular modulation method. We demonstrate that using triethylamine as a modulator results in a conspicuous decrease in elastic modulus (0.7 ± 0.2 GPa) compared to the unmodified nanocrystals of ZIF-8 (2.1 ± 0.8 GPa). Argon gas adsorption analysis also reveals that the more flexible, amine-modified framework exhibited gradual and cooperative gate-opening structural transitions (P/P0 = 0.33 ± 0.02) compared to the steep and stepwise characteristics of unmodified samples of ZIF-8 (P/P0 = 0.45 ± 0.02). The differences in Argon gas pressure-induced structural deformations correspond to the decrease in elastic modulus of base-modified nanocrystals of ZIF-8, likely a consequence of the impact of Et3N on the relative number of point defects and hydrogen bonds in the framework. Our study demonstrates how a combination of AFM nanoindentation, gas uptake, and spectroscopic characterization can be applied to understand structural and energetic changes upon adsorption in flexible framework materials.
Isothermal stress and elasticity tensors for ions and point dipoles using Ewald summations (2005)

The isothermal stress tensor and isothermal elasticity tensor for systems of point charges and of nonpolarizable point dipoles are derived from the strain derivatives of the free energy. For the case of point dipoles, it is shown that the angular dependence of the interaction potential gives rise to additional contributions to the stress and elasticity tensors not recognized previously.
Data from Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma (2023)

&lt;div&gt;Abstract&lt;p&gt;Pediatric glioblastoma (pGBM) is a lethal cancer with no effective therapies. To understand the mechanisms of tumor evolution in this cancer, we performed whole-genome sequencing with linked reads on longitudinally resected pGBM samples. Our analyses showed that all diagnostic and recurrent samples were collections of genetically diverse subclones. Clonal composition rapidly evolved at recurrence, with less than 8% of nonsynonymous single-nucleotide variants being shared in diagnostic-recurrent pairs. To track the origins of the mutational events observed in pGBM, we generated whole-genome datasets for two patients and their parents. These trios showed that genetic variants could be (i) somatic, (ii) inherited from a healthy parent, or (iii) &lt;i&gt;de novo&lt;/i&gt; in the germlines of pGBM patients. Analysis of variant allele frequencies supported a model of tumor growth involving slow-cycling cancer stem cells that give rise to fast-proliferating progenitor-like cells and to nondividing cells. Interestingly, radiation and antimitotic chemotherapeutics did not increase overall tumor burden upon recurrence. These findings support an important role for slow-cycling stem cell populations in contributing to recurrences, because slow-cycling cell populations are expected to be less prone to genotoxic stress induced by these treatments and therefore would accumulate few mutations. Our results highlight the need for new targeted treatments that account for the complex functional hierarchies and genomic heterogeneity of pGBM.&lt;/p&gt;Significance:&lt;p&gt;This work challenges several assumptions regarding the genetic organization of pediatric GBM and highlights mutagenic programs that start during early prenatal development.&lt;/p&gt;&lt;/div&gt;
Synthesis of Lipid-α-End-Functionalized Chains by RAFT Polymerization. Stabilization of Lipid/Polymer Particle Assemblies (2008)

A functional dithioester including a phospholipid moiety (Lipid-DT) has been synthesized in a high yield (71% after purification) from a precursor chain transfer agent (CTA) and fully characterized. The RAFT polymerization of an acrylamide derivative, N-acryloylmorpholine (NAM), mediated by this Lipid-DT exhibits a prolonged induction period in comparison with a nonfunctional dithioester. This phenomenon is discussed in terms of steric shielding induced by the bulky lipid moiety of the CTA. Moreover, the lipid moiety located at the α-end of the chains has a strong influence on the size exclusion chromatography analyses in THF using a standard-based calibration, with the suspicion of a retention phenomenon. The well-defined structure of the lipid-end-functionalized polymer chains has been evidenced by MALDI−TOF mass spectrometry. Finally, these chains have been successfully incorporated into lipid/polymer particle assemblies (LipoParticles) that resulted in an improved stabilization in aqueous medium at relatively high ionic strength (300 mM).
Three Dimensional NMR Microscopy Towards In Vivo Cellular Imaging (2005)

Recent advances in NMR microscopy are discussed with applications to the study of single cell development. Fundamental resolution limit due to molecular diffusion as well as experimental resolution limits arising from system bandwidth and poor signal-to-noise ratio due to small image voxel size arc studied. Finite line broadening due to the signal attenuation by diffusion are also investigated. Several microscopic imaging pulse sequences to maximize signal-to-noise ratio as well as tissue dependent contrast are presented and applied to elucidate cellular imaging such as the cell lineage patterns in Xenopus luevis embryos. Experimental results obtained with 7.0 Tesla NMR microscopy system are presented.
Supramolecular motifs in dynamic covalent PEG-hemiaminal organogels (2015)

Dynamic covalent materials are stable materials that possess reversible behaviour triggered by stimuli such as light, redox conditions or temperature; whereas supramolecular crosslinks depend on the equilibrium constant and relative concentrations of crosslinks as a function of temperature. The combination of these two reversible chemistries can allow access to materials with unique properties. Here, we show that this combination of dynamic covalent and supramolecular chemistry can be used to prepare organogels comprising distinct networks. Two materials containing hemiaminal crosslink junctions were synthesized; one material is comprised of dynamic covalent junctions and the other contains hydrogen-bonding bis-hemiaminal moieties. Under specific network synthesis conditions, these materials exhibited self-healing behaviour. This work reports on both the molecular-level detail of hemiaminal crosslink junction formation as well as the macroscopic behaviour of hemiaminal dynamic covalent network (HDCN) elastomeric organogels. These materials have potential applications as elastomeric components in printable materials, cargo carriers and adhesives.
Convenient synthesis of substituted pyrroles via a cerium (IV) ammonium nitrate (CAN)-catalyzed Paal–Knorr reaction (2013)

A screening of various cerium salts for promoting the Paal–Knorr pyrrole synthesis revealed the superiority of cerium (IV) ammonium nitrate (CAN) as a catalyst. Excellent yields of substituted pyrroles were obtained in CAN-catalyzed Paal–Knorr reactions of 1,4-diketones with various amines. The protocol is noteworthy for the mild reaction condition, short reaction times, scalability and easy isolation of products and high yields of the products.
Reply (2011)

Sir:Figure“Prospective protocols and data-driven analyses are essential to continually reevaluate emerging trends in breast cancer patient care.” The partial reiteration of this sentence from our article noted above omits the key concept that patients with early-stage breast cancer are a “… heterogenous patient population ….” This of course requires individualized patient treatment planning and selection that are essential to providing optimized cancer control. In the effort to eradicate cancer, our treatments often have undesirable severe adverse consequences on quality of life. With increasing use of postmastectomy radiation therapy in early breast cancer, many medical centers and surgeons have reverted to a policy of only performing delayed reconstruction in these patients because of the increasing use postmastectomy radiation therapy in this patient population. These patients lose the benefit of skin-sparing mastectomy and have to awake from mastectomy without a breast, like patients treated long ago who routinely presented for much more advanced breast cancers. To address this situation, the technique of “delayed-immediate” breast reconstruction was developed to allow patients with early-stage breast cancer to continue to be able to awake from mastectomy with a breast, receive the aesthetic benefit of skin-sparing mastectomy, and avoid radiation damage to the definitive breast reconstruction.1 This multidisciplinary approach to breast reconstruction uses a two-stage approach. Patients who are determined preoperatively by our multidisciplinary breast team to be at an increased risk for requiring postmastectomy radiation therapy have a tissue expander placed at mastectomy to preserve the breast skin envelope. Patients who are subsequently found not to require postmastectomy radiation therapy after review of the permanent pathologic sections undergo definitive reconstruction using the preserved breast skin. However, those who are determined to require postmastectomy radiation therapy have the expander partially deflated for postmastectomy radiation therapy, then reinflated after postmastectomy radiation therapy, and then proceed to definitive autogenous reconstruction 3 months after completion of postmastectomy radiation therapy. Prospective protocols and data-driven analyses are essential to continually reevaluate emerging trends in patient care, particularly in patients with early-stage breast cancer. Historically, questioning treatment strategies in breast cancer has led to major advances for women with this disease. We are clearly in an era of individualized care for breast cancer patients, and the need for postmastectomy radiation therapy should be individualized to those who will receive a significant benefit and not routinely administered to a heterogeneous group of patients. Steven J. Kronowitz, M.D. Henry M. Kuerer, M.D., Ph.D. University of Texas M. D. Anderson Cancer Center, Houston, Texas
Transgenic Marine Microalgae: A Value‐Enhanced Fishmeal and Fish Oil Replacement (2013)

Fishmeal had been a major feed source, mainly for monogastric animals, as well as dairy cattle, and is required for many fish species in aquaculture, and fish oil is a major source of omega-3 fatty acids. Due to diminishing fish stocks, it is being replaced by vegetable protein supplemented with synthetic amino acids. Transgenically domesticated algae could be engineered to be enriched in specific amino acids, have improved digestibility, and contain replacements for expensive feed additives, becoming a cost-effective replacement for fishmeal and fish oil. The enrichment must be in algae engineered to obtain stable, contamination-free cultures that are transgenically mitigated to be unable to survive outside of cultivation. If culture conditions can be rendered cost-effective, such cultures could compete with soybeans/oil palm and be the next technological breakthrough to overcome Malthus' predictions of insufficient food for humanity, as the feed material can be cultivated on desert lands or floating on bodies of water, using seawater and thus augmenting agriculture without competing for land and freshwater.
Cu‐Catalyzed Asymmetric Conjugate Additions of Dialkyl‐ and Diarylzinc Reagents to Acyclic β‐Silyl‐α,β‐unsaturated Ketones. Synthesis of Allylsilanes in High Diastereo‐ and Enantiomeric Purity. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Quantitative ultrasound, elastography, and machine learning for assessment of steatosis, inflammation, and fibrosis in chronic liver disease (2022)

Random forest models incorporating QUS and shear wave elastography increased the classification accuracy of liver steatosis, inflammation, and fibrosis when compared to shear wave elastography alone.
A Quantitative Proteomics Analysis of Subcellular Proteome Localization and Changes Induced by DNA Damage (2009)

A major challenge in cell biology is to identify the subcellular distribution of proteins within cells and to characterize how protein localization changes under different cell growth conditions and in response to stress and other external signals. Protein localization is usually determined either by microscopy or by using cell fractionation combined with protein blotting techniques. Both these approaches are intrinsically low throughput and limited to the analysis of known components. Here we use mass spectrometry-based proteomics to provide an unbiased, quantitative, and high throughput approach for measuring the subcellular distribution of the proteome, termed "spatial proteomics." The spatial proteomics method analyzes a whole cell extract created by recombining differentially labeled subcellular fractions derived from cells in which proteins have been mass-labeled with heavy isotopes. This was used here to measure the relative distribution between cytoplasm, nucleus, and nucleolus of over 2,000 proteins in HCT116 cells. The data show that, at steady state, the proteome is predominantly partitioned into specific subcellular locations with only a minor subset of proteins equally distributed between two or more compartments. Spatial proteomics also facilitates a proteome-wide comparison of changes in protein localization in response to a wide range of physiological and experimental perturbations, shown here by characterizing dynamic changes in protein localization elicited during the cellular response to DNA damage following treatment of HCT116 cells with etoposide. DNA damage was found to cause dissociation of the proteasome from inhibitory proteins and assembly chaperones in the cytoplasm and relocation to associate with proteasome activators in the nucleus.
Stereochemistry of phospho transfer catalyzed by bovine liver acid phosphatase. (1981)

The hydrolysis of phosphoric monoesters by acid phosphatases is thought to proceed via the formation of a phosphoenzyme intermediate, but no stereochemical evidence exists on this point. We have carried out the transphosphorylation from phenyl (R)-[16O, 17O, 18O] phosphate to (S)-propane-1,2-diol in the presence of homogeneous bovine liver acid phosphatase, and have found that the reaction proceeds with greater 90% overall retention of configuration at phosphorus. This stereochemical course of phospho transfer during the enzyme-catalyzed reaction of the phosphoric monoester is consistent with a double displacement mechanism in which each step proceeds with inversion of the stereochemistry at phosphorus, and is similar to the behavior of the bacterial alkaline phosphatase.
Organic and Amorphous-Metal-Oxide Flexible Analogue Electronics (2018)

Recent years have witnessed significant research efforts in flexible organic and amorphous-metal-oxide analogue electronics, in view of its formidable potential for applications such as smart sensor systems. This Element provides a comprehensive overview of this growing research area. After discussing the properties of organic and amorphous-metal-oxide technologies relevant to analogue circuits, this Element focuses on their application to two key circuit blocks: amplifiers and analogue-to-digital converters. The Element thus provides a fresh look at the evolution and immediate opportunities of the field, and identifies the remaining challenges for these technologies to become the platform of choice for flexible analogue electronics.