Scaffolding Catalysis: Towards Regioselective Hydroformylation of Alkenes and Site-Selective Functionalization of Polyhydroxylated Molecules

Thesis advisor: Kian L. TanChapter 1. We reported the first synthesis of all-carbon quaternary centers via hydroformylations using a catalytic directing group. With the ability of reversibly and covalently binding to a substrate, and coordinating to a metal center, scaffolding catalyst 1.1 is able to direct the branch-selective hydroformylation of 1,1-disubstituted olefins under mild temperature. Chapter 2. We have designed and synthesized a chiral organocatalyst 2.11. This catalyst is able to covalently bind to one hydroxyl, and utilize the induced intramolecularity to stereoselectively functionalize the other hydroxyl within a cis-1,2-diol via electrophile transfer. Catalyst 2.11 was used in the desymmetrization of meso-1,2-diols under mild conditions (4 C to room temperature), leading to high yields and selectivities for a broad substrate scope. Chapter 3. Catalyst 3.1 and 3.6 were demonstrated to selectively bind to primary hydroxyls over secondary hydroxyls. By combining the binding selectivity with asymmetric catalysis, these scaffolding catalysts were shown to promote the selective silylation of secondary hydroxyls within terminal (S)-1,2-diols. The reversal of substrate bias was further applied to a regiodivergent kinetic resolution of racemic terminal 1,2-diols, producing secondary protected products in synthetically practical levels of enantioselectivity (>95:5 er) and yields (≥40%). Time course studies of this reaction further revealed the optimal condition to form the primary silylated product in high s-factor. Chapter 4. Based on the previous understanding of catalyst 4.5 and 4.6, the exclusive catalyst recognition of cis-1,2-diols within polyhydroxylated molecules was further discovered. This unique functional group display recognition was further allied with the catalyst's ability to stereoselectively differentiate hydroxyls within cis-1,2-diols, enabling the site-selective protection, functionalization, and activation of the inherently less reactive axial hydroxyl groups within carbohydrates. This methodology also enables the selective functionalization of multiple complex molecules, including digoxin, mupirocin, and ribonucleosides, demonstrating the potential power of scaffolding catalysis in the rapid access to valuable synthetic derivatives of polyhydroxylated compounds.Thesis (PhD) — Boston College, 2013.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Chemistry

iLoRE: Dynamic Graph Representation with Instant Long-term Modeling and Re-occurrence Preservation

Continuous-time dynamic graph modeling is a crucial task for many real-world applications, such as financial risk management and fraud detection. Though existing dynamic graph modeling methods have achieved satisfactory results, they still suffer from three key limitations, hindering their scalability and further applicability. i) Indiscriminate updating. For incoming edges, existing methods would indiscriminately deal with them, which may lead to more time consumption and unexpected noisy information. ii) Ineffective node-wise long-term modeling. They heavily rely on recurrent neural networks (RNNs) as a backbone, which has been demonstrated to be incapable of fully capturing node-wise long-term dependencies in event sequences. iii) Neglect of re-occurrence patterns. Dynamic graphs involve the repeated occurrence of neighbors that indicates their importance, which is disappointedly neglected by existing methods. In this paper, we present iLoRE, a novel dynamic graph modeling method with instant node-wise Long-term modeling and Re-occurrence preservation. To overcome the indiscriminate updating issue, we introduce the Adaptive Short-term Updater module that will automatically discard the useless or noisy edges, ensuring iLoRE's effectiveness and instant ability. We further propose the Long-term Updater to realize more effective node-wise long-term modeling, where we innovatively propose the Identity Attention mechanism to empower a Transformer-based updater, bypassing the limited effectiveness of typical RNN-dominated designs. Finally, the crucial re-occurrence patterns are also encoded into a graph module for informative representation learning, which will further improve the expressiveness of our method. Our experimental results on real-world datasets demonstrate the effectiveness of our iLoRE for dynamic graph modeling

Graph Prompt Learning: A Comprehensive Survey and Beyond

Artificial General Intelligence (AGI) has revolutionized numerous fields, yet its integration with graph data, a cornerstone in our interconnected world, remains nascent. This paper presents a pioneering survey on the emerging domain of graph prompts in AGI, addressing key challenges and opportunities in harnessing graph data for AGI applications. Despite substantial advancements in AGI across natural language processing and computer vision, the application to graph data is relatively underexplored. This survey critically evaluates the current landscape of AGI in handling graph data, highlighting the distinct challenges in cross-modality, cross-domain, and cross-task applications specific to graphs. Our work is the first to propose a unified framework for understanding graph prompt learning, offering clarity on prompt tokens, token structures, and insertion patterns in the graph domain. We delve into the intrinsic properties of graph prompts, exploring their flexibility, expressiveness, and interplay with existing graph models. A comprehensive taxonomy categorizes over 100 works in this field, aligning them with pre-training tasks across node-level, edge-level, and graph-level objectives. Additionally, we present, ProG, a Python library, and an accompanying website, to support and advance research in graph prompting. The survey culminates in a discussion of current challenges and future directions, offering a roadmap for research in graph prompting within AGI. Through this comprehensive analysis, we aim to catalyze further exploration and practical applications of AGI in graph data, underlining its potential to reshape AGI fields and beyond. ProG and the website can be accessed by \url{https://github.com/WxxShirley/Awesome-Graph-Prompt}, and \url{https://github.com/sheldonresearch/ProG}, respectively

The latest spreading periods of the south china sea: new constraints from macrostructure analysis of IODP expedition 349 cores and geophysical data

Author Posting. © American Geophysical Union, 2019. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research-Solid Earth 124 (2019): 9980– 9998, doi:10.1029/2019JB017584.Macrostructures preserved in deformed rocks are essential for the understanding of their evolution, especially when the deformation is weak and hard to discriminate in regional scale or purely through geophysical data. In order to resolve the inconsistency between NS trending fracture zones and NE oriented spreading fabrics of the South China Sea during the latest spreading stage, we analyzed macrostructures identifiable from the basalt and consolidated sediment samples of the Integrated Ocean Drilling Program (IODP) Sites U1431 and U1433. These two sites are close to the East and Southwest relict spreading ridges and provide critical information on the latest spreading stages. The structures in the basalt of both sites suggest two dominant orientations of NS and NE. At U1431, sediments show mainly WNW trending slickensides, different from that of basalt. At U1433, no structures were found in postspreading sediment. Thus, NE and NS trending structures in basalt are most possibly formed by seafloor spreading. Crosscutting relationship suggests that NE trending structures formed first, followed by NS and finally WNW trending structures. These observations are consistent with geophysical features. Magnetic anomalies and ocean bottom seismometer velocity suggest that the latest relict ridge of the East Subbasin coincides with the EW trending seamount chain. Located between the relict ridges of East and Southwest Subbasins, NS trending Zhongnan‐Liyue Fracture Zone had acted as the latest transform fault. Based on the above evidences, we proposed that the South China Sea may have experienced a short period of NS oriented spreading after earlier SE spreading. These results resolve the previous inconsistencies.We appreciate Anne Replumaz and other anonymous reviewers for the constructive suggestions, which improve this paper to a great extent. This research was supported by Guangdong NSF research team project (2017A030312002), K. C. Wong Education Foundation (GJTD‐2018‐13), the IODP‐China Foundation, the NSFC Projects (91628301, 41376027, 41576070, 41576068, 41430962, 41674069, 91528302, and 20153410), U.S. National Science Foundation through Grant EAR‐1250444, the Guangdong Province Foundation (41576068), and the Joint Foundation of the Natural Science Foundation of China (NSFC) and Guangdong Province (U1301233). Fucheng Li is thanked for helping with the earthquake epicenter figure for the study area. All the sample photos can be accessed via web address (http://www.iodp.tamu.edu). The archive halves of samples are kept in the Kochi repository. The paleomag data will be published by Xixi Zhao separately. All the other geophysical data have been published; for example, the multichannel seismic could be referenced to Li et al. (2015a), and the gravity data and magnetic anomaly data are from Sandwell et al. (2014) and Ishihara and Kisimoto (1996).2020-02-2

Effects of Hydrological and Climatic Variables on Cyanobacterial Blooms in Four Large Shallow Lakes Fed by the Yangtze River

Shallow lakes, one of the most widespread water bodies in the world, are easily shifted to a new trophic state due to external interferences. Shifting hydrologic conditions and climate change can cause cyanobacterial harmful algal blooms (CyanoHABs) in shallow lakes, which pose serious threats to ecological integrity and human health. This study analyzed the effects of hydrologic and meteorological variables on cyanobacterial blooms in Yangtze-connected lakes (Lake Dongting and Poyang) and isolated lakes (Lake Chao and Tai). The results show that (i) chlorophyll-a (Chl-a) concentration tends to decrease exponentially with increasing relative lake level fluctuations (RLLF) and precipitation, but to increase linearly with increasing wind speed and air temperature; (ii) Chl-a concentrations in lakes were significantly higher when RLLF \u3c 100, precipitation \u3c 2.6 mm, wind speed \u3e 2.6 m s−1, or air temperature \u3e 17.8 °C; (iii) the Chl-a concentration of Yangtze-isolated lakes was more significantly affected by water level amplitude, precipitation, wind speed and air temperature than the Yangtze-connected lakes; (iv) the RLLF and the ratio of wind speed to mean water depth could be innovative coupling factors to examine variation characteristics of Chl-a in shallow lakes with greater correlation than single factors

A multimodal fusion method for Alzheimer’s disease based on DCT convolutional sparse representation

IntroductionThe medical information contained in magnetic resonance imaging (MRI) and positron emission tomography (PET) has driven the development of intelligent diagnosis of Alzheimer’s disease (AD) and multimodal medical imaging. To solve the problems of severe energy loss, low contrast of fused images and spatial inconsistency in the traditional multimodal medical image fusion methods based on sparse representation. A multimodal fusion algorithm for Alzheimer’ s disease based on the discrete cosine transform (DCT) convolutional sparse representation is proposed.MethodsThe algorithm first performs a multi-scale DCT decomposition of the source medical images and uses the sub-images of different scales as training images, respectively. Different sparse coefficients are obtained by optimally solving the sub-dictionaries at different scales using alternating directional multiplication method (ADMM). Secondly, the coefficients of high-frequency and low-frequency subimages are inverse DCTed using an improved L1 parametric rule combined with improved spatial frequency novel sum-modified SF (NMSF) to obtain the final fused images.Results and discussionThrough extensive experimental results, we show that our proposed method has good performance in contrast enhancement, texture and contour information retention

B Cell-Related Circulating MicroRNAs With the Potential Value of Biomarkers in the Differential Diagnosis, and Distinguishment Between the Disease Activity and Lupus Nephritis for Systemic Lupus Erythematosus

Our understanding of circulating microRNAs (miRNAs) related to systemic lupus erythematosus (SLE) remains very limited. In this study, we screened SLE-specific miRNAs in plasma from 42 B cell-related miRNAs by using miRNA PCR Array. The selected miRNAs were first confirmed in plasma samples from 50 SLE patients, 16 rheumatoid arthritis (RA) patients, and 20 healthy donors using qRT-PCR. We then investigated the relationship between expressions of the selected miRNAs and SLE clinical indicators. As a result, 14 miRNAs (miR-103, miR-150, miR-20a, miR-223, miR-27a, miR-15b, miR-16, miR-181a, miR-19b, miR-22, miR-23a, miR-25, miR-92a, and miR-93) were significantly decreased in the plasma of SLE patients compared with healthy controls (P < 0.05) and could act as the diagnostic signature to distinguish SLE patients from healthy donors. Six miRNAs (miR-92a, miR-27a, miR-19b, miR-23a, miR-223, and miR-16) expressed in plasma were significantly lower in SLE patients than in RA patients (P < 0.05), revealing the potentially diagnostic signature to distinguish SLE patients from RA patients. Furthermore, the downregulated expression of miR-19b, miR-25, miR-93, and miR-15b was associated with SLE disease activity (P < 0.05) while miR-15b and miR-22 expressions were significantly lower in SLE patients with low estimate glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) (P < 0.05). The diagnostic potential of miR-15b for SLE disease activity and lupus nephritis (LN) with low eGFR was validated on an independent validation set with 69 SLE patients and a cross-validation set with 80 SLE patients. In summary, the signature of circulating miRNAs will provide novel biomarkers for the diagnosis of SLE and evaluation of disease activity and LN

Seismic stratigraphy of the central South China Sea basin and implications for neotectonics

Coring/logging data and physical property measurements from International Ocean Discovery Program Expedition 349 are integrated with, and correlated to, reflection seismic data to map seismic sequence boundaries and facies of the central basin and neighboring regions of the South China Sea. First-order sequence boundaries are interpreted, which are Oligocene/Miocene, middle Miocene/late Miocene, Miocene/Pliocene, and Pliocene/Pleistocene boundaries. A characteristic early Pleistocene strong reflector is also identified, which marks the top of extensive carbonate-rich deposition in the southern East and Southwest Subbasins. The fossil spreading ridge and the boundary between the East and Southwest Subbasins acted as major sedimentary barriers, across which seismic facies changes sharply and cannot be easily correlated. The sharp seismic facies change along the Miocene-Pliocene boundary indicates that a dramatic regional tectonostratigraphic event occurred at about 5 Ma, coeval with the onsets of uplift of Taiwan and accelerated subsidence and transgression in the northern margin. The depocenter or the area of the highest sedimentation rate switched from the northern East Subbasin during the Miocene to the Southwest Subbasin and the area close to the fossil ridge in the southern East Subbasin in the Pleistocene. The most active faulting and vertical uplifting now occur in the southern East Subbasin, caused most likely by the active and fastest subduction/obduction in the southern segment of the Manila Trench and the collision between the northeast Palawan and the Luzon arc. Timing of magmatic intrusions and seamounts constrained by seismic stratigraphy in the central basin varies and does not show temporal pulsing in their activities.Keywords: South China Sea, Neotectonism, Core-well-seismic integration, Seismic facies, Seismic stratigraphy, IODP Expedition 34

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat