The Ohio State University

The drive for higher per-lane data rates has led to increased complexity in wireline transceiver architectures due to the need for higher-order equalization. This has the potential to result in degraded energy and area efficiency of these transceivers. A new multi-stage decision feedback equalizer (DFE) design approach that leverages speculative intersymbol interference (ISI) cancellation to achieve low complexity is proposed. A 2-tap multi-stage PAM4 DFE design example that uses lower than 35 $\%$ of the components of a conventional speculative DFE, and can be applied to most channel profiles, is used to discuss the equalization capability of the proposed approach. It is also used to discuss the impact of circuit nonidealities on performance. Simulation results of the multi-stage DFE over three different channels showed matched equalization performance to the conventional designs, even as it promises higher data rates than the direct feedback DFE and drastically higher energy efficiency than the conventional speculative DFE.

Emerging medium-voltage silicon carbide devices offer the potential to achieve more efficient and compact power electronics for grid-tied applications. However, the lack of an effective insulation solution for packaging the devices has slowed their widespread adoption. Recently, a nonlinear resistive polymer nanocomposite coating has been introduced to enhance the insulation by reducing localized electric field stress inside the modules. The purpose of this study is to evaluate the insulation capability of the polymer nanocomposite under high dv/dt. Half-bridge modules of 15-kV silicon carbide devices were packaged with the nanocomposite coating at the triple points on the module substrate. All the modules were tested free of partial discharge at 20 kV for 1 min. One module underwent a repetitive double-pulse test at 10 kV, 2A and was switching at a peak dv/dt > 300 V/ns. These findings further support the coating's potential as a viable practical solution to the insulation challenge of medium-voltage power modules.

During cell invasion, large Extracellular Vesicle (lEV) release from host cells was dose‐dependently triggered by Trypanosoma cruzi metacyclic trypomastigotes (Mtr). This lEV release was inhibited when IP3‐mediated Ca²⁺ exit from the ER and further Ca²⁺ entry from plasma membrane channels was blocked, but whilst any store‐independent Ca²⁺ entry (SICE) could continue unabated. That lEV release was equally inhibited if all entry from external sources was blocked by chelation of external Ca²⁺ points to the major contributor to Mtr‐triggered host cell lEV release being IP3/store‐mediated Ca²⁺ release, SICE playing a minor role. Host cell lEVs were released through Mtr interaction with host cell lipid raft domains, integrins, and mechanosensitive ion channels, whereupon [Ca²⁺]cyt increased (50 to 750 nM) within 15 s. lEV release and cell entry of T. cruzi, which increased up to 30 and 60 mpi, respectively, as well as raised actin depolymerization at 60 mpi, were all reduced by TRPC inhibitor, GsMTx‐4. Vesicle release and infection was also reduced with RGD peptide, methyl‐β‐cyclodextrin, knockdown of calpain and with the calpain inhibitor, calpeptin. Restoration of lEV levels, whether with lEVs from infected or uninfected epithelial cells, did not restore invasion, but supplementation with lEVs from infected monocytes, did. We provide evidence of THP‐1 monocyte‐derived lEV interaction with Mtr (lipid mixing by R18‐dequenching; flow cytometry showing transfer to Mtr of R18 from R18‐lEVs and of LAP(TGF‐β1). Active, mature TGF‐β1 (at 175 pg/×10⁵ in THP‐1 lEVs) was detected in concentrated lEV‐/cell‐free supernatant by western blotting, only after THP‐1 lEVs had interacted with Mtr. The TGF‐β1 receptor (TβRI) inhibitor, SB‐431542, reduced the enhanced cellular invasion due to monocyte‐lEVs.

Background The lifetime risk of pancreatic cancer in women with a germline mutation in BRCA1 and BRCA2 is not well established. In an international prospective cohort of female carriers of BRCA1 and BRCA2 mutations, the cumulative incidence of pancreatic cancer from age 40 until 80 years was estimated. Methods A total of 8295 women with a BRCA1 or BRCA2 mutation were followed for new cases of pancreatic cancer. Subjects were followed from the date of baseline questionnaire or age 40 years (whichever came last) until a new diagnosis of pancreatic cancer, death from another cause, or date of last follow‐up. Results Thirty‐four incident pancreatic cancer cases were identified in the cohort. The annual risk of pancreatic cancer between age 40 and 80 years was 0.04% for BRCA1 carriers and 0.09% for BRCA2 carriers. Via the Kaplan–Meier method, the cumulative incidence from age 40 to 80 years was 2.2% (95% CI, 1.1%–4.3%) for BRCA1 carriers and 2.7% (95% CI, 1.3%–5.4%) for BRCA2 carriers. Only two of the 34 cases reported a first‐degree relative with pancreatic cancer (hazard ratio, 4.75; 95% CI, 1.13–19.9; p = .03). Risk factors for pancreatic cancer included alcohol intake and a history of diabetes. The 5‐year survival rate for the 34 cases was 8.8%. Conclusions The lifetime risk of pancreatic cancer is approximately 2% in women with a BRCA1 mutation and 3% for women with a BRCA2 mutation. The poor survival in hereditary pancreatic cancer underscores the need for novel antitumoral strategies.

As the field of theranostics expands, an imminent need arises for multifaceted polymer‐based nanotechnologies for clinical application. In this work, reversible addition‐fragmentation chain transfer (RAFT) aqueous emulsion polymerization is used to form ¹⁹ F‐containing amphiphilic hybrid block copolymers (HBCs). Employing a cationic dendritic macromolecular chain transfer agent (mCTA), polymer frameworks comprised of chemically distinctive blocks of differing architectures (i.e., dendritic and grafted/linear) are strategically designed and synthesized. In aqueous media, self‐assembled polymer nanoparticles (PNPs) are formed. Their physicochemical properties and their potential as biomaterials for MRI applications are assessed. By showcasing a newly established mCTA and using these resulting PNPs as imaging probes, the work expands the design space of RAFT polymerization in biomedical research, paving the way for the development of more effective and versatile MRI imaging tools.

The Groundwater Module within the Sustainability Nexus Analytics, Informatics, and Data (AID) Programme of the United Nations University (UNU) addresses critical challenges in sustainable groundwater management. Groundwater resources around the world are under increasing stress from overextraction and pollution, threatening water and food security for billions. Groundwater governance is not one-dimensional but multi-faceted, and central to the management of environmental, social, and economic systems worldwide. In line with the Nexus Approach, the goal of the UNU Sustainability Nexus AID Programme's Groundwater Module is improving access to data and information tools that help scientists and decision-makers address interdisciplinary groundwater problems that affect humans and nature. Here, we describe the critical need for a Nexus Approach to groundwater-related issues and highlight current challenges involving data and information gaps and data-model operability. The Groundwater Module can help address these challenges by offering a central hub for data, analytics, and informatics for addressing groundwater-related issues. By integrating dispersed datasets and modeling tools, this module aims to enable analysis and new insights. We showcase some of the tools in the Groundwater Module and discuss future opportunities in the global pursuit to fulfill the UN Sustainable Development Goals (SDGs).

Radiation therapy is a cornerstone in the treatment of central nervous system (CNS) tumors, with brachytherapy offering a unique and advantageous approach by placing localized radiation sources within tumors or resection sites. Despite its potential, brachytherapy’s utility is clouded by the diversity in radiation sources, techniques, and trial designs. This chapter aims to clarify consistent themes, delve into radiobiological and physics principles, explore isotope applications, and provide an overview of brachytherapy techniques, empowering clinicians, and researchers to make informed decisions when considering it as a treatment option. Drawing from available data, in this chapter, we summarize its effectiveness across various CNS sites and malignancies.

Stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hfSRT) using linear accelerators (LINACs) have become increasingly common treatment modalities for intracranial neoplasms. This chapter provides an overview of the history, principles, techniques, clinical applications, and quality assurance considerations for LINAC-based SRS and hfSRT. The evolution of LINAC technology and treatment planning capabilities have enabled high-quality SRS and hfSRT treatments that are dosimetrically equivalent to Gamma Knife radiosurgery, even for complex cases like multiple brain metastases. Frameless immobilization, high-resolution image guidance, and six degree of freedom alignment have facilitated precise and efficient treatments. Clinical evidence supports the use of LINAC-based SRS and hfSRT for various benign and malignant intracranial tumors, with high rates of local control and acceptable toxicity. A comprehensive quality assurance program is essential to ensure safe and effective radiosurgical treatments. As indications for SRS continue to expand and more radiotherapy centers adopt these techniques, LINAC-based SRS and hfSRT will play an increasingly important role in the management of intracranial neoplasms.

The Ohio Corn Performance Test (OCPT) aims to provide farmers, educators, agronomists, and seed companies with information to help growers make decisions regarding hybrid selection and increase overall crop productivity. For more than 50 years, the OCPT has evaluated the agronomic performance of commercially available corn hybrids across the state. The objective of this study was to highlight overall trends as they relate to crop management, agronomic performance, and grain yields. The program has been planted annually at about 10 distinct sites grouped in three regions: Southwest/West Central Region, Northwest Region, and North Central/Northeast Region. Data collection and measurements include crop emergence percentages, lodging ratings, grain moisture, volumetric grain weight, and grain yields. Over the last 50 years, more than 53,000 hybrid combinations (i.e., hybrids × environments × years) were tested in the OCPT. From 1972 to 2021, seeding rates increased from 68,259 to 89,239 seeds ha⁻¹, seedling emergence increased from 86.2% to 94.9%, and final plant stands increased from 58,559 to 84,649 plants ha⁻¹. From these trends, the number of days from planting to harvest decreased by 11.5 days (slightly later planting dates, variable harvest dates), grain moisture at harvest decreased by 48 g kg⁻¹, and average volumetric grain weight increased by 83 kg m⁻³. The same period had a grain yield gain of 0.135 Mg ha⁻¹ year⁻¹, with 9.09 Mg ha⁻¹ in 1972 and 16.97 Mg ha⁻¹ in 2021 (an 87% increase). Overall, the annual OCPT results show agronomic and yield improvements that have contributed to the selection of hybrids in the state of Ohio.

Objective This study examined children at the onset of tic disorder (tics for less than 9 months: NT group), a population on which little research exists. Here, we investigate relationships between the baseline shape and volume of subcortical nuclei, diagnosis, and tic symptom outcomes. Methods 187 children were assessed at baseline and a 12-month follow-up: 88 with NT, 60 tic-free healthy controls (HC), and 39 with chronic tic disorder/Tourette syndrome (TS), using T1-weighted MRI and total tic scores (TTS) from the Yale Global Tic Severity Scale to evaluate symptom change. Subcortical surface maps were generated using FreeSurfer-initialized large deformation diffeomorphic metric mapping. Linear regression models correlated baseline structural shapes with follow-up TTS while accounting for covariates, with relationships mapped onto structure surfaces. Results We found that the NT group had a larger right hippocampus compared to HC. Surface maps illustrate distinct patterns of inward deformation in the putamen and outward deformation in the thalamus for NT compared to controls. We also found patterns of outward deformation in almost all studied structures when comparing the TS group to controls. The NT group also showed consistent outward deformation compared to TS in the caudate, accumbens, putamen, and thalamus. Subsequent analyses including clinical symptoms revealed that a larger pallidum and thalamus at baseline correlated with less improvement of tic symptoms at follow-up. Conclusion These observations constitute some of the first prognostic biomarkers for tic disorders and suggest that these subregional shape and volume differences may be associated with the outcome of tic disorders.

The structures of [Fe(CO)3(η⁴-6-exo-(tri-m-tolylphosphine)cyclohepta-2,4-dien-1-one][BF4] [tetragonal, a = 35.6005(7), b = 35.6005(7), c = 10.5456(3), space group I41/a] and [Fe(CO)3(η⁴-6-exo-(tri-p-fluorophenylphosphine)cyclohepta-2,4-dien-1-one][BF4] [triclinic, a = 9.8852(3), b = 10.0996(4), c = 16.0526(4), α = 99.813(3), β = 94.164(2), g = 102.911(3) space group P-1] have been determined. Both structures contain a disordered CH2Cl2 molecule. The tetrafluoroborate ion in [Fe(CO)3(η⁴-6-exo-(tri-m-tolylphosphine)cyclohepta-2,4-dien-1-one][BF4] is also disordered. There are no close contacts indicative of hydrogen bonding within either structure, but there is π-π stacking observed for [Fe(CO)3(η⁴-6-exo-(tri-m-tolylphosphine)cyclohepta-2,4-dien-1-one][BF4]. Graphical Abstract Addition of PAr3 (Ar = m-C6H4CH3 or p-C6H4F) to [Fe(CO)3(η⁵-cyclohepta-2,4-dien-5-yl-1-one)][BF4] results in attack at the coordinated ring in a position exo- to the iron atom forming the corresponding [Fe(CO)3(η⁴-6-exo-(PAr3)cyclohepta-2,4-dien-1-one][BF4] compounds, which were structurally characterized

Background The outcome of kidney transplant recipients with a history of complement-mediated thrombotic microangiopathy (cTMA) and those who develop post-transplant de novo TMA (dnTMA) is largely unknown. Methods We retrospectively studied all kidney transplant recipients with end-stage kidney disease secondary to cTMA and those who developed dnTMA, between Jan 2000 and Dec 2020 in our center. Results We identified 134 patients, 22 with cTMA and 112 had dnTMA. Patients with cTMA were younger at the time of TMA diagnosis (age at diagnosis, 28.9 ± 16.3. vs 46.5 ± 16.0 years; P < 0.001). T-cell mediated rejection, borderline rejection, and calcineurin inhibitor toxicity were more prevalent in the first kidney transplant biopsy (P < 0.05) in the dnTMA group, and antibody-mediated rejection was more prevalent in anytime-biopsy (P = 0.027). After adjusting for potential confounders, cTMA was associated with a sixfold increase in the hazard of transplant failure during the first-year post-transplant (adjusted hazard ratio (aHR): 6.37 [95%CI: 2.17 to18.68; P = 0.001]; the aHR decreased by 0.87 (95% CI: 0.76 to 0.99: P = 0.033) per year elapsed since transplantation. Long-term allograft survival was similar in both groups. Conclusion Post kidney transplant TMA is an important cause of poor allograft survival. More studies are needed to enhance our understanding and management of this disorder.

Wildfires emit solid-state strongly absorptive brown carbon (solid S-BrC, commonly known as tar ball), critical to Earth’s radiation budget and climate, but their highly variable light absorption properties are typically not accounted for in climate models. Here, we show that from a Pacific Northwest wildfire, over 90% of particles are solid S-BrC with a mean refractive index of 1.49 + 0.056i at 550 nm. Model sensitivity studies show refractive index variation can cause a ~200% difference in regional absorption aerosol optical depth. We show that ~50% of solid S-BrC particles from this sample uptake water above 97% relative humidity. We hypothesize these results from a hygroscopic organic coating, potentially facilitating solid S-BrC as nuclei for cloud droplets. This water uptake doubles absorption at 550 nm and the organic coating on solid S-BrC can lead to even higher absorption enhancements than water. Incorporating solid S-BrC and water interactions should improve Earth’s radiation budget predictions.

Introduction This study applied a novel tobacco regulatory science paradigm to characterize inter-product variation in the appeal and sensory features of emerging commercial and therapeutic oral nicotine products (ONPs) among young adults that vape e-cigarettes. Methods Twenty-three young adults without ONP experience who use e-cigarettes completed a single-blind, single-visit remote lab study. Participants rated appeal and sensory characteristics during 5-minute standardized self-administrations of 8 ONPs (4 fruit, 4 mint) from various brands (Lucy, Rouge, Solace, Nicorette, On!, Velo). Participants were randomized between-subjects to ONP type (pouches or gum). Results Gum ONPs were rated sweeter (B = 19.5, 95% CI = 4.3, 34.7), stronger in flavor (B = 25.6, 95% CI = 12.2, 39.0), and lower in tingling sensation (B = -14.0, 95% CI = -27.8, -0.2) than pouches. Fruit-flavored ONPs were sweeter (B = 12.9, 95% CI = 6.1, 19.7) and caused less burning (B = -12.0, 95% CI = -19.5, -4.5) than mint. Product type x flavor interactions found that gum vs. pouch enhanced sweetness and flavor strength more for fruit than mint, while pouch vs. gum increased burning and harshness more for mint. Nicorette White Ice was most appealing, while Rogue Fruit and Nicorette Mint were less so. Appeal correlated with most types of sensory experiences (rs = -.33-.54), except for tingling and burning. Conclusions Nicotine gums may offer a more pleasant sensory experience than pouches for young adults who use e-cigarettes, with variation across brand/flavor variants. Implications Results indicate that gum ONPs and fruit flavors may offer greater appeal and a more pleasant sensory experience than pouch ONPs and mint flavors for young adults who use e-cigarettes and are ONP-naïve, with heterogeneity in user experience across some brand/flavor variants. This study also introduces a method for assessing the appeal and sensory features of ONPs, which can inform regulatory efforts and strategies to reduce nicotine dependence among young adults who use e-cigarettes.

Inhalation exposure to airborne fine particulate matter (aerodynamic diameter < 2.5 µm, PM 2.5 ) is known to cause metabolic dysfunction-associated steatohepatitis (MASH) and the associated metabolic syndrome. Hepatic lipid accumulation and inflammation are the key characteristics of MASH. However, the mechanism by which PM 2.5 exposure induces lipid accumulation and inflammation in the liver remains to be further elucidated. In this study, we revealed that inhalation exposure to PM 2.5 induces nitrosative stress in mouse livers by suppressing hepatic S-nitrosoglutathione reductase (GSNOR) activities, which leads to S-nitrosylation modification of the primary unfolded protein response (UPR) transducer IRE1α, an endoplasmic reticulum (ER)-resident protein kinase and endoribonuclease (RNase). S-nitrosylation suppresses RNase activity of IRE1α and subsequently decreases IRE1α-mediated splicing of the mRNA encoding X-box binding protein 1 (Xbp1) and IRE1α-dependent degradation of select microRNAs (miRNAs), including miR-200 family, miR-34, miR-223, miR-155, and miR-146, in the livers of the mice exposed to PM 2.5 . Elevation of IRE1α-target miRNAs, due to impaired IRE1α RNase activity by PM 2.5 -triggered S-nitrosylation, leads to decreased expression of the major regulators of fatty acid oxidation, lipolysis and anti-inflammatory response, including XBP1, SIRT1, PPARα, and PPARγ, in the liver, which account at least partially for hepatic lipid accumulation and inflammation in mice exposed to airborne PM 2.5 . In summary, our study revealed a novel pathway by which PM 2.5 causes cytotoxicity and promotes MASH-like phenotypes through inducing hepatic nitrosative stress and S-nitrosylation of the primary UPR transducer and subsequent elevation of select miRNAs involved in metabolism and inflammation in the liver.