Changes In Poly Research Articles

Design of Dual Winding Flux Modulation Machine for Performance Improvement in Variable Speed Application

In this paper, a Dual Winding Flux Modulation Machine (DWFMM) is proposed for variable speed application. The DWFMM is configured by adding windings to the Single Winding Flux Modulation Machine (SWFMM), consisting of a master winding that drives the motor and a slave winding that enables pole changing and performance enhancement. Through pole changing, the DWFMM can operate as two different machines: a Vernier Machine (VM) for varying speeds and torque operations and a Permanent Magnet Synchronous Machine (PMSM). In the VM mode, flux enhancement is applied to improve torque, and in the PMSM mode, Flux Weakening is applied to increase speed. The characteristics of the two different operating modes were analyzed using the Finite Element Method (FEM) to validate the machine’s performance. Finally, the DWFMM and SWFMM were designed and compared as variable speed application machines to confirm their suitability and superiority.

The Role of the Polyethylene Glycol in the Organization of Gold Nanorods at the Air-Water and Air-Solid Interfaces.

The organization of metallic nanoparticles into assembled films is a complex process. The type of nanoparticle stabilizing ligand and the method for creating an organized layer can profoundly affect the optical properties of the resulting nanoparticle assembly. Investigations of the ligand structure and nanoparticle interactions can provide a greater understanding of the design of the assembly process and the quality of the resulting materials. One of the functionalization methods in the preparation of specific gold nanorods is the utilization of thiol-terminated poly(ethylene glycol). This generates gold nanorods capable of forming stable monolayers at the air-water interface upon dispersion in a suitable organic solvent. Herein, we show that depending on the molecular weight of the poly(ethylene glycol), the structures obtained at the air-water and air-solid interfaces differ in the arrangement. The studied structures were characterized by using spectroscopic and microscopic techniques, and the structural type was correlated with the polymer type. Insoluble and stable Langmuir monolayers composed of higher-molecular-weight gold nanorods with poly(ethylene glycol) were formed only in the presence of an additional stabilizer that prevented the formation of gold nanorods in aqueous solutions. At the air-solid interface, conformational changes in poly(ethylene glycol) induced the aggregation of gold nanorods, which became closely packed under the influence of surface pressure. The presented results suggested that the arrangement of two-dimensional layers of gold nanorods could be tailored using poly(ethylene glycol) of various molecular weights.

Abstract 6222: Exposing the heterogeneity of the lipidome in the TME of cutaneous melanoma following treatment with NUC-7738 in combination with anti-PD-1 therapy

Abstract Background. Malignant melanoma exhibits distinct lipid profiles compared to normal tissue and changes in the lipidome influence multiple aspects of tumor biology. Lipidomic alterations within the tumor microenvironment (TME) may influence the efficacy of anti-PD-1 therapy. In combination with anti-PD-1 agent pembrolizumab, NUC-7738 (3'-deoxyadenosine [3’-dA] which is phosphorylated and protected with a phosphoramidate moiety attached at the 5’-position) has shown promising activity in anti-PD-1 refractory melanoma (Phase 2; NCT03829254). NUC-7738 generates sustained intracellular levels of 3’-dATP, which profoundly alters RNA regulatory processes in tumor cells, resulting in impaired cellular responses and changes in expression of proteins related to lipid biosynthesis. To interrogate components of the TME before and after NUC-7738 + pembrolizumab treatment, we developed a novel workflow incorporating Mass Spectrometry Imaging (MSI) to co-register lipidomic changes with molecular markers. Machine learning accelerated the interpretation of complex data obtained from paired patient biopsies. Methods. Snap frozen paired biopsies from patients with advanced cutaneous melanoma treated with NUC-7738 ±pembrolizumab were analyzed by desorption electrospray ionization (DESI)-MSI. Specific metabolic (e.g., ASAH1) and immune (e.g., CD8, CD20) markers were investigated by multiplex immunofluorescence (mIF) post DESI-MSI. Target selection was guided by bulk RNA-seq data. Raw MSI data was visualized using Waters HDI® software. Data extracted from selected regions of interest was exported into MetaboAnalyst 5.0 for statistical analysis. LIPID MAPS® Structure Database was used to assign lipid species. mIF/mIHC images were analyzed by HALO® AI. Results. Single 10 µm tissue sections allowed co-registered DESI-MSI and mIF, suitable for further informatic and AI-enabled image analysis. This facilitated direct comparison of lipids, cells, and protein expression in the TME, before and after treatment with NUC-7738, a compound known to cause profound changes in poly(A) tail regulation. MSI data analyses of the TME uncovered intra-tumoral heterogeneity of the lipidome and demonstrated changes following treatment. Conclusion. This platform provides a powerful investigative tool to simultaneously explore the myriad of factors in the TME that contribute to tumorigenesis and therapeutic response. Further analyses of the role of the lipidome in the TME and intra-tumoral heterogeneity will be explored in paired biopsies from patients with PD-1 inhibitor refractory melanoma. Citation Format: Alison L. Dickson, Greice M. Zickuhr, In Hwa Um, Ying Zhang, Ruth Plummer, Sarah P. Blagden, Stefan N. Symeonides, Natalie Cook, T.R. Jeffry Evans, Mustafa Elshani, David J. Harrison. Exposing the heterogeneity of the lipidome in the TME of cutaneous melanoma following treatment with NUC-7738 in combination with anti-PD-1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6222.

A pole-changing flux reversal permanent magnet motor

In this paper, a pole-changing (PC) flux reversal permanent magnet (FRPM) motor is proposed for obtaining a wide speed range. According to the general air-gap field modulation theory, the permanent magnet (PM) magnetic field is modulated into a series of harmonics with different pole numbers by rotor teeth. By introducing an especial PM arrangement, two groups of working harmonics with different pole-pair numbers are generated in the proposed 12-7 PC-FRPM motor due to the modulation of rotor teeth. Based on the calculated slot pitch angles of these harmonics, two winding connections can be obtained for PC operation to achieve two operating modes. The electromagnetic performance of PC-FRPM motor before and after PC are analyzed using finite element analysis and verified by the experimental test results.

Astronomically forced paleoclimate and sea-level changes recorded in the continental margin of the South China Sea over the past ∼23 m.y.

The Earth has witnessed the emergence of continental-sized ice sheets, starting with Antarctica and gradually extending to both hemispheres over the past 40 million years. These ice accumulations have had a dramatic impact on both paleoclimate and sea level, substantially influencing sediment deposition in the continental margins. However, understanding sediment accumulation on an orbital scale in continental margins remains limited because of the scarcity of high-resolution, chronologically constrained sedimentary records. Here, we conducted a highly resolved cyclostratigraphic analysis based on natural gamma radiation (GR) series in depth domain at the continental margin of the South China Sea. We established a 22.8 m.y.-long high-resolution astronomical time scale spanning from the Miocene to the Quaternary by tuning the GR records to the global deep-sea benthic foraminifera carbon isotope curves and the 405 k.y. eccentricity cycles. The m.y.-scale sea-level changes since the Miocene were reconstructed through the sedimentary noise modeling of the 405-k.y.-tuned GR series. These reconstructions aligned with regional and global sea-level changes. The phase correlation between the filtered 1.2 m.y. cycles of sea-level change curves (dynamic noise after orbital tuning and ρ1 median models) from δ13Cbenthic and tuned GR series and the 1.2 m.y. obliquity amplitude modulation cycles revealed a shift from an anti-phase to an in-phase relationship across the middle Miocene climate transition (ca. 13.8 Ma), suggesting extensive expansion of the Antarctic ice sheet played a key role. In addition, a shift from an in-phase to an anti-phase relationship during the late Miocene (ca. 8 Ma and 5.3 Ma), indicating ephemeral expansion of the Arctic ice sheets or the changes in carbon cycle involving the terrestrial and deep ocean carbon reservoirs, might be the primary driver of eustatic changes. Furthermore, obliquity forcing and changes in meridional gradients in insolation that transported poleward flux of heat, moisture, and precipitation increased ice accumulation in both pole ice sheets and nonlinearly transferred high-latitude signals to low-latitude regions. This phenomenon is supported by the observation of strong obliquity signals in low latitude during global climate cooling interval. Our results suggest that m.y.-scale sea-level variations respond to astronomically induced climate change and ice sheet dynamics of both poles. This work contributes a highly resolved low-latitude geological archive to the future reconstruction of paleoclimate evolution on a global scale.

Finite Element Analysis of a Three Speed Induction Machine

This paper deals with the Finite Element (FE) analysis of a special Three Speed Squirrel Cage Induction Machine (TSSCIM) with pole changing stator windings. Compared to classical multi-speed induction machines, the studied TSSCIM is designed so as to change in the same time the number of pole pairs (p) and the number of stator phases (m) so as to keep constant the product p x m. The numerical model of the machine used in this study is based on a 2D plane-parallel finite element approach and aims at finding some of the main steady state operation characteristics of the machine working both as motor and generator for three different running speeds. A comparison of the proposed TSSCIM with a classical inverter fed squirrel cage induction machine is also presented in order to underline some advantages and disadvantages of each solution.

Cosolvent-Induced Gating and Structural Changes in Poly(ethylene oxide)-Grafted Gold Nanopores

Cosolvent-Induced Gating and Structural Changes in Poly(ethylene oxide)-Grafted Gold Nanopores

Design and Optimization of a Pole Changing Flux Switching Permanent Magnet Motor

A flux switching permanent magnet (FSPM) motor is designed and optimized in this paper to achieve high torque density and expanded speed regulation range from a design viewpoint of pole-changing (PC). Based on the field modulation theory, the PM field in the FSPM motor is modulated by the stator and rotor teeth, generating rich harmonics with different pole-pair numbers in the air-gap flux density. By adopting an appropriate slot pole combination, working harmonics with different slot pitch angles are obtained to establish a basis of the PC-FSPM motor. Then, different working harmonics can be used to achieve different energy conversions with different winding configurations, so the PC operation can be performed to realize the high torque and wide speed regulation range by switching the working modes. Based on the field modulation theory, the operation principle of conventional and PC-FSPM motors are analyzed and compared. Then, according to the design principle of the PC-FSPM motor, a 24/22-pole PC-FSPM motor with the E-core is designed and optimized by a multi-level optimization method. Finally, the electromagnetic performances are analyzed by finite element analysis and the test results of the prototype have verified the feasibility of the motor.

Conformational Changes of Poly(Maleic Anhydride-alt-styrene) Modified with Amino Acids in an Aqueous Medium and Their Effect on Cytocompatibility and Hemolytic Response.

The conformational changes of poly(maleic anhydride-alt-styrene) (PSMA) modified with different amino acids (PSMA-Aa) were studied in an aqueous medium as a function of ionic strength and pH. The specific viscosity of PSMA-Aa decreased with increasing salt concentration due to a more compact conformation. There was a decrease in surface tension with increasing concentrations of the modified polyelectrolyte having a greater effect for the PSMA modified with l-phenylalanine at pH 7.0, demonstrating a greater surface-active character. The conformational changes were also confirmed by molecular dynamics studies, indicating that PSMA-Aa exhibits a compact structure at pH 4.0 and a more extended structure at pH 7.0. On the other hand, the conformational changes of PSMA-Aa were related to its biological response, where the higher surface-active character of the PSMA modified with l-phenylalanine correlates very well with the higher hemolytic activity observed in red blood cells, in which the surface-active capacity supports lytic potency in erythrocytes. The cytocompatibility assays indicated that there were no significant cytotoxic effects of the PSMA-Aa. Additionally, in solvent-accessible surface area studies, it was shown that the carboxylate groups of the PSMA modified with l-phenylalanine are more exposed to the solvent at pH 7.0 and high salt concentrations, which correlates with lower fluorescence intensity, reflecting a loss of mitochondrial membrane potential. It is concluded that the study of the conformational changes in PE modified with amino acids is essential for their use as biomaterials and relevant to understanding the possible effects of PE modified with amino acids in biological systems.

Terahertz spectroscopy of interchain hydrogen bond changes of poly (L-lactic acid)/poly (D-lactic acid) blends during solution crystallization

The blending of poly (L-lactic acid) (PLLA) and poly (D-lactic acid) (PDLA) achieves an effective transformation of properties based on the formation of interchain hydrogen bonds. Therefore, it is important to study the stereo-complex (SC) system. We studied the solution crystallization of PLLA/PDLA blends based on the sensitivity of terahertz (THz) spectroscopy to hydrogen bonds. The results revealed an abnormal red-shift in the characteristic peak frequency of the blends with the increase of PLLA, which is attributed to the difference in chain stacking of the main components in the blends. Moreover, we believe that the peak height of the SC at 1.43 THz is an accurate index reflecting the interchain hydrogen bonds in the case of blending ratio changes. When the blend ratio is determined, we found that the blue shift of this peak frequency corresponded to the weakening of interchain hydrogen bonds. The results show that THz spectroscopy can effectively observe the solution crystallization behavior of blends, and its different characteristic indexes contain the information of interaction and aggregation structure.

Comparison of chlorination resistance of biodegradable microplastics and conventional microplastics during the disinfection process in water treatments

Nowadays, microplastics (MPs) widely exist in the environment, and water treatment plants are important sources of MPs. Chlorine is widely used in the disinfection process in water treatment plants and has strong oxidation, however, the chemical and physical properties changes of MPs during chlorination were unclear. Thus, in this study, based on the actual used chlorine concentrations, different chlorination conditions were simulated to study the variation of MPs after chlorination. Meanwhile, the produced disinfection by-products were monitored. The results showed that under high chlorination concentration conditions, functional groups of polyethylene (PE), polystyrene (PS), and polylactic acid (PLA) changed, while no peak shift or change of poly (butyleneadipate-co-terephthalate) (PBAT) could be detected. Moreover, after chlorination, partial yellowing and cracks appeared on PS, PLA, and PBAT, while PE remained white and showed little morphological changes. Besides, chlorination led to the narrowing of the cold crystallization peak and melting peak of PLA, while chlorination had little influence on the crystal structure of PE and PBAT. Furthermore, the reaction between PLA and chlorine mostly produced more trichloromethane than other types of MPs. Consequently, when chlorine concentrations were in the range of 2.5 to 5000 mg/L, the chlorination resistance was PBAT/PE > PLA > PS. Specifically, PBAT had the strongest chlorination resistance in terms of chemical properties, while PE had the strongest chlorination resistance in terms of physical properties. Therefore, the degradability of biodegradable MPs is not higher than that of conventional MPs in all cases. Moreover, it should be noted that most changes occurred only in high chlorine concentrations. Thus, neither conventional MPs nor biodegradable MPs can be completely degraded during the chlorination process in water treatments.

The origin of the Musicians Seamount Province and its inferences for Late Cretaceous Pacific Plate Motion

Linear chains of seamounts, sourced from mantle plume processes, have the potential to refine plate motion models because the hotspot remains fixed relative to the moving lithospheric plate. However, to define plate motion, consistent seamount age progression and geometry are required. Some seamount chains, such as the Musician Seamount Province (MSP), have complex geometries and age distributions, which complicates calibrating plate motion. The MSP resides northwest of the Hawaiian Islands and is composed of seamounts and volcanic elongated ridges (VERs) that cover ∼420,000 km2 of Pacific seafloor. Here we provide new 40Ar/39Ar age determinations for a series of lava flows recovered from the MSP during expedition EX1708 of the National Oceanic and Atmospheric Administration's Ocean Exploration program. The MSP was built by four distinct volcanic processes: (1) age-progressive hotspot volcanism associated with the Euterpe Plume (ca. 98–79 Ma). (2) VER formation from plume-ridge channelization (ca. 97–94 Ma; 86–79 Ma) where the VERs only form when the hotspot is within ∼600 km of the ridge. (3) Eocene volcanism driven by extension during the ca. 50 Ma change in Pacific rotation poles (ca. 54–47 Ma). (4) Some near-ridge shear-driven upwelling or diffuse extensional volcanism that preceded the southern MSP lithosphere overriding the plume (ca. 86–84 Ma). By filtering lava flows with only robust statistically concordant 40Ar/39Ar age determinations as well as geologic setting, we develop a dataset of samples valuable for constraining Pacific plate motion. A local plate velocity of 42 ± 9 km/Ma for the 98–81 Ma time frame is calculated. Furthermore, the seamount track indicates that large shifts in Pacific rotation pole locations are required prior to 98 Ma and at ca. 81 Ma.

Pole-Transition Control of Variable-Pole Machines Using Harmonic-Plane Decomposition

Variable phase-pole machines have the potential to extend the operational range to higher speeds through magnetic pole changes. The state-of-the-art vectorspace decomposition cannot model the transient behavior of the pole change for any possible phase-pole configuration as it creates a discontinuity. The proposed harmonicplane decomposition theory solves this issue by generalizing the vector-space decomposition to the fullest extend by using its discrete Fourier transformation interpretation. The theory for indirect rotor field-oriented control is developed using the harmonic-plane decomposition. A controlled, loaded pole change on a wound independently-controlled stator-coils machine using two transition strategies shows the harmonic-plane decomposition-based controller's ability to maintain torque in the transition. Additionally, the proposed controller accomplishes real harmonic injection and balanced steady-state operation.

A unique poly(A) tail profile uncovers the stability and translational activation of TOP transcripts during neuronal differentiation

Cell differentiation is associated with global changes in translational activity. Here, we characterize how mRNA poly(A) tail processing supports this dynamic. We observe that decreased translation during neuronal differentiation of P19 cells correlates with the downregulation of 5'-terminal oligopyrimidine (TOP) transcripts which encode the translational machinery. Despite their downregulation, TOP transcripts remain highly stable and show increased translation as cells differentiate. Changes in TOP mRNA metabolism are reflected by their accumulation with poly(A) tails ∼60-nucleotide (nt) long. The dynamic changes in poly(A) processing can be partially recapitulated by depleting LARP1 or activating the mTOR pathway in undifferentiated cells. Although mTOR-induced accumulation of TOP mRNAs with tails ∼60-nt long does not trigger differentiation, it is associated with reduced proliferation of neuronal progenitors. We propose that while TOP mRNAs are transcriptionally silenced, their post-transcriptional regulation mediated by a specific poly(A) processing ensures an adequate supply of ribosomes to complete differentiation.

Mechanical Properties, Morphological Characteristics and Microstructural Changes of Poly(glycolide-co-ε-caprolactone-co-l-lactide) Suture during In Vitro Degradation

Mechanical Properties, Morphological Characteristics and Microstructural Changes of Poly(glycolide-co-ε-caprolactone-co-l-lactide) Suture during In Vitro Degradation

Developing 3D-network gels from polysaccharide gums for biomedical applications

Keeping in view the recent advancements in polysaccharide materials, gum acacia (GA) - tragacanth gum (TG) was investigated for designing polymeric network structures impregnated with cephalexin antibiotics for drug delivery (DD). Grafted product of polyvinylimidazole [poly(VIm)] and GA-TG was characterized by field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Change in mesh size (from 17.73 to 32.98 nm) and crosslinking density (between 1.64 × 10−5 to 5.06 × 10−5 mol cm−3) was found with change in poly(VIm), gum and crosslinker NNMBA content which revealed that these parameters can be tailored made as per requirement and applications. Swelling properties illustrated pH sensitivity in copolymers because of composition which is useful for colon or site-specific DD of cephalexin. FESEM and AFM demonstrated heterogeneous morphology with the rough surface topology of grafted product. XPS and FTIR confirmed the grafting of poly(VIm) onto polysaccharide chains. Drug diffusion was non-Fickian and release was fitted in Higuchi kinetic model from copolymers. The release was slow and prolonged due to drug-polymer interactions. Copolymers exhibited 31.29% scavenging ability in DPPH assay and haemolysis was less than 2% that inferred biocompatible nature. Bio-surface interactions with intestinal membrane indicated the muco-adhesive nature of copolymers. Antimicrobial properties of hydrogel were evaluated against E. coli, P. aeruginosa and S. aureus. All observations revealed that GA-TG crosslinked copolymers could be explored for colon DD of antibiotic drugs with tailored crosslinking density.

Prediction of herpes virus infections after solid organ transplantation: a prospective study of immune function.

Herpes virus infections are a major concern after solid organ transplantation and linked to the immune function of the recipient. We aimed to determine the incidence of positive herpes virus (cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1/2 (HSV-1/2), and varicella zoster virus (VZV)) PCR tests during the first year post-transplantation and assess whether a model including immune function pre-transplantation and three months post-transplantation could predict a subsequent positive herpes virus PCR. All participants were preemptively screened for CMV, and EBV IgG-negative participants were screened for EBV during the first year post-transplantation. Herpes virus PCR tests for all included herpes viruses (CMV, EBV, HSV-1/2, and VZV) were retrieved from the Danish Microbiology database containing nationwide PCR results from both hospitals and outpatient clinics. Immune function was assessed by whole blood stimulation with A) LPS, B) R848, C) Poly I:C, and D) a blank control. Cytokine concentrations (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α, and IFN-γ) were measured using Luminex. We included 123 liver (54%), kidney (26%), and lung (20%) transplant recipients. The cumulative incidence of positive herpes virus PCR tests was 36.6% (95% CI: 28.1-45.1) during the first year post-transplantation. The final prediction model included recipient age, type of transplantation, CMV serostatus, and change in Poly I:C-induced IL-12p40 from pre-transplantation to three months post-transplantation. The prediction model had an AUC of 77% (95% CI: 61-92). Risk scores were extracted from the prediction model, and the participants were divided into three risk groups. Participants with a risk score <5 (28% of the cohort), 5-10 (45% of the cohort), and >10 (27% of the cohort) had a cumulative incidence of having a positive herpes virus PCR test at 5.8%, 25%, and 73%, respectively (p < 0.001). In conclusion, the incidence of positive herpes virus PCR tests was high, and a risk model including immune function allowed the prediction of positive herpes virus PCR and may be used to identify recipients at higher risk.

Calculation of no‐load induced electromotive force of pole changing line‐start permanent magnet synchronous motor

AbstractPole changing line‐start permanent magnet synchronous motor (LSPMSM) can significantly improve the starting capability of LSPMSM by decreasing the braking torque and pulsating torque during starting process. The fundamental reason for the elimination of braking torque is that there is no generating effect during minor‐pole starting process. That is to say, induced electromotive force (EMF) does not exist when the magnetic field generated by multi‐pole rotor PMs cut the minor‐pole stator winding. Therefore, the induced EMF of pole changing LSPMSM is analysed theoretically and calculated analytically. Considering that the magnetic flux per pole of the coils under the adjacent pole are different, the induced EMFs of a conductor, a full‐pitch coil, a coil group in minor‐pole stator winding are, respectively, calculated, and then the general analytical expression of the induced EMF of a phase winding with different rotor/stator pole ratio is derived. Then, the motors with different rotor/stator pole ratios are simulated based on finite element method to obtain the corresponding EMFs. Meanwhile, a 6/8 pole changing LSPMSM is taken as prototype. The consistency of the simulation, experiment, and the analytical calculation results effectively verify the validity of the derived general analytical expression and theoretical analysis.

Large Supplements of Nicotinic Acid and Nicotinamide Increase Tissue NAD+ and Poly(ADP-Ribose) Levels but Do Not Affect Diethylnitrosamine-Induced Altered Hepatic Foci in Fischer-344 Rats

Poly(ADP-ribose) is a homopolymer of ADP-ribose units synthesized from NAD+ on nuclear acceptor proteins and is known to be involved in DNA repair. It is not known whether large oral doses of the clinically utilized NAD precursors nicotinic acid or nicotinamide affect poly(ADP-ribose) metabolism or the cellular response to DNA damage. In our first study, using Fischer-344 rats, 2 wk of dietary nicotinic acid supplementation (500 and 1000 mg/kg diet) caused elevated levels of NAD+ in the blood, liver, heart and kidney, while nicotinamide caused elevated levels only in the blood and liver, compared with controls fed a diet containing 30 mg/kg nicotinic acid. Both nicotinic acid and nicotinamide, at 1000 mg/kg diet, caused elevations in liver NAD+, by 44 and 43%, respectively. Only nicotinamide, however, elevated liver poly(ADP-ribose) (63% higher than control group). Following treatment with the hepatocarcinogen diethylnitrosamine, higher levels of hepatic NAD+ were observed in rats fed both nicotinic acid and nicotinamide at 1000 mg/kg diet, but only nicotinic acid supplementation caused a greater accumulation of hepatic poly(ADP-ribose) (61% higher than control group). Neither of the dietary treatments significantly affected the proportion of the liver occupied by placental glutathione-S-transferase positive foci. These results show that poly(ADP-ribose) synthesis is not directly responsive to hepatic NAD+ levels during niacin supplementation, and that the mechanisms of action of nicotinic acid and nicotinamide are different. The observed changes in poly(ADP-ribose) metabolism do not appear to cause any change in susceptibility to chemically induced carcinogenesis in this organ.

Macrophage differentiation is marked by increased abundance of the mRNA 3' end processing machinery, altered poly(A) site usage, and sensitivity to the level of CstF64.

Regulation of mRNA polyadenylation is important for response to external signals and differentiation in several cell types, and results in mRNA isoforms that vary in the amount of coding sequence or 3' UTR regulatory elements. However, its role in differentiation of monocytes to macrophages has not been investigated. Macrophages are key effectors of the innate immune system that help control infection and promote tissue-repair. However, overactivity of macrophages contributes to pathogenesis of many diseases. In this study, we show that macrophage differentiation is characterized by shortening and lengthening of mRNAs in relevant cellular pathways. The cleavage/polyadenylation (C/P) proteins increase during differentiation, suggesting a possible mechanism for the observed changes in poly(A) site usage. This was surprising since higher C/P protein levels correlate with higher proliferation rates in other systems, but monocytes stop dividing after induction of differentiation. Depletion of CstF64, a C/P protein and known regulator of polyadenylation efficiency, delayed macrophage marker expression, cell cycle exit, attachment, and acquisition of structural complexity, and impeded shortening of mRNAs with functions relevant to macrophage biology. Conversely, CstF64 overexpression increased use of promoter-proximal poly(A) sites and caused the appearance of differentiated phenotypes in the absence of induction. Our findings indicate that regulation of polyadenylation plays an important role in macrophage differentiation.