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At least 19 records

Inhibition of the proton-activated chloride channel PAC by PIP 2

Proton-activated chloride (PAC) channel is a ubiquitously expressed pH-sensing ion channel, encoded by PACC1 (TMEM206). PAC regulates endosomal acidification and macropinosome shrinkage by releasing chloride from the organelle lumens. It is also found at the cell surface, where it is activated under pathological conditions related to acidosis and contributes to acid-induced cell death. However, the pharmacology of the PAC channel is poorly understood. Here, we report that phosphatidylinositol (4,5)-bisphosphate (PIP 2 ) potently inhibits PAC channel activity. We solved the cryo-electron microscopy structure of PAC with PIP 2 at pH 4.0 and identified its putative binding site, which, surprisingly, locates on the extracellular side of the transmembrane domain (TMD). While the overall conformation resembles the previously resolved PAC structure in the desensitized state, the TMD undergoes remodeling upon PIP 2 -binding. Structural and electrophysiological analyses suggest that PIP 2 inhibits the PAC channel by stabilizing the channel in a desensitized-like conformation. Our findings identify PIP 2 as a new pharmacological tool for the PAC channel and lay the foundation for future drug discovery targeting this channel.

59 BASIC BIOLOGICAL SCIENCES↗

PAC in DESI. I. Galaxy stellar mass function into the 10 6 M ⊙ frontier

The Photometric objects Around Cosmic webs (PAC) method integrates cosmological photometric and spectroscopic surveys, offering valuable insights into galaxy formation. PAC measures the excess surface density of photometric objects, $\bar{n}_2w_{{\rm {p}}}$, with specific physical properties around spectroscopic tracers. In this study, we improve the PAC method to make it more rigorous and eliminate the need for redshift bins. We apply the enhanced PAC method to the DESI Y1 BGS Bright spectroscopic sample and the deep Dark Energy Camera Legacy Survey (DECaLS) photometric sample, obtaining $\bar{n}_2w_{{\mathrm {p}}}$ measurements across the complete stellar mass range, from $10^{5.3}$ to $10^{11.5}\,{\rm M}_{\odot }$ for blue galaxies, and from $10^{6.3}$ to $10^{11.9}\,{\rm M}_{\odot }$ for red galaxies. We combine $\bar{n}_2w_{{\rm {p}}}$ with $w_{{\rm {p}}}$ measurements from the BGS sample, which is not necessarily complete in stellar mass. Assuming that galaxy bias is primarily determined by stellar mass and colour, we derive the galaxy stellar mass functions (GSMFs) down to $10^{5.3}\,{\rm M}_{\odot }$ for blue galaxies and $10^{6.3}\,{\rm M}_{\odot }$ for red galaxies, while also setting lower limits for smaller masses. The blue and red GSMFs are well described by single and double Schechter functions, respectively, with low-mass end slopes of $\alpha _{\rm {blue}}=-1.54^{+0.02}_{-0.02}$ and $\alpha _{\rm {red}}=-2.50^{+0.08}_{-0.08}$, resulting in the dominance of red galaxies below $10^{7.6}\,{\rm M}_{\odot }$. Stage-IV cosmological photometric surveys, capable of reaching 2–3 mag deeper than DECaLS, present an opportunity to explore the entire galaxy population in the local universe with PAC. This advancement allows us to address critical questions regarding the nature of dark matter, the physics of reionization, and the formation of dwarf galaxies.

79 ASTRONOMY AND ASTROPHYSICS↗

Photometric Objects around Cosmic Webs (PAC) Delineated in a Spectroscopic Survey. I. Methods

We provide a method for estimating the projected density distribution ${\bar{n}}_{2}{w}_{p}({r}_{p})$ of photometric objects around spectroscopic objects in a spectroscopic survey. This quantity describes the distribution of photometric sources with certain physical properties (e.g., luminosity, mass, and color) around cosmic webs (PAC) traced by the spectroscopic objects. The method can make full use of current and future deep and wide photometric surveys to explore the formation of galaxies up to medium redshift (z s < 2) 3 with the aid of cosmological spectroscopic surveys that sample only a fairly limited species of objects (e.g., emission line galaxies). As an example, we apply the PAC method to the CMASS spectroscopic and HSC-SSP PDR2 photometric samples to explore the distribution of galaxies for a wide range of stellar masses from 10 9.0 to 10 12.0 M ⊙ around massive galaxies at z s ≈ 0.6. Using the abundance-matching method, we model ${\bar{n}}_{2}{w}_{p}({r}_{p})$ in N-body simulation using Markov chain Monte Carlo sampling, and we accurately measure the stellar–halo mass relation and stellar mass function for the whole mass range. We can also measure the conditional stellar mass function of satellites for central galaxies of different mass. The PAC method has many potential applications for studying the evolution of galaxies.

79 ASTRONOMY AND ASTROPHYSICS↗

Photometric Objects Around Cosmic Webs (PAC) Delineated in a Spectroscopic Survey. III. Accurate Measurement of Galaxy Stellar Mass Function with the Aid of Cosmological Redshift Surveys

We present a novel method to accurately measure the galaxy stellar mass function (GSMF) based upon the Photometric objects Around Cosmic webs (PAC) method developed in our first paper (Paper I) of the series. The method allows us to measure the GSMF to a lower-mass end that is not accessible to the spectroscopic sample used in the PAC. Compared with Paper I, the current measurement of GSMF is direct and model independent. We measure the GSMFs in the redshift ranges of z$^{3}_{s}$ < 0.2, 0.2 < z s < 0.4, and 0.5 < z s < 0.7 down to stellar masses of M* = 10 8.2 , 10 10.6 , and 10 10.6 M ⊙ , using the data from the Dark Energy Spectroscopic Instrument (DESI) Legacy Imaging Surveys and the spectroscopic samples of Slogan Digital Sky Survey (i.e., Main, LOWZ, and CMASS samples). Our results show that there is no evolution of GSMF from z s = 0.6 to z s = 0.1 for M* > 10 10.6 M ⊙ , and that there is a clear upturn at M* ≈ 10 9.5 M ⊙ toward smaller galaxies in the local GMSF at z s = 0.1. We provide an accurate double Schechter fit to the local GSMF for the entire range of M* and a table of our measurements at the three redshifts, which can be used to test theories of galaxy formation. Our method can achieve an accurate measurement of GSMF to the stellar mass limit where the spectroscopic sample is already highly incomplete (e.g., ~ 10 -3 ) for its target selection.

79 ASTRONOMY AND ASTROPHYSICS↗

Materials Data on PaC by Materials Project

PaC is Halite, Rock Salt structured and crystallizes in the cubic Fm-3m space group. The structure is three-dimensional. Pa4+ is bonded to six equivalent C4- atoms to form a mixture of corner and edge-sharing PaC6 octahedra. The corner-sharing octahedral tilt angles are 0°. All Pa–C bond lengths are 2.54 Å. C4- is bonded to six equivalent Pa4+ atoms to form a mixture of corner and edge-sharing CPa6 octahedra. The corner-sharing octahedral tilt angles are 0°.

36 MATERIALS SCIENCE↗

PAC in DESI. II. Galaxy-halo connection into the $10^{6}{\rm M}_{\odot}$ frontier

Understanding dwarf galaxy formation is crucial for testing dark matter models and reionization physics. However, constructing stellar-mass complete spectroscopic samples at low masses is increasingly difficult, and the potential existence of a local void complicates studies in an average environment. The Photometric object Around Cosmic webs (PAC) method, which combines deep photometric and spectroscopic data to measure the excess surface density $\bar{n}_2w_{\rm{p}}(r_{\rm{p}})$ of photometric objects around spectroscopic tracers, offers a promising path forward. We model 349 $\bar{n}_2w_{\rm{p}}(r_{\rm{p}})$ measurements from DESI Y1 BGS and DECaLS, reaching $M_*=10^{6.4}\,{\rm M}_{\odot}$, using a stellar mass-halo mass relation (SHMR)-based subhalo abundance matching framework applied to two high-resolution $N$-body simulations from the Jiutian suite. The resulting SHMR is constrained down to $M_{\rm h}\simeq10^{8.0}\,h^{-1}{\rm M}_{\odot}$, revealing a clear upturn at $\sim10^{10.0}\,h^{-1}{\rm M}_{\odot}$ toward lower masses, indicating rising star-formation efficiency (SFE) in small haloes. This feature persists under extensions of the model that allow mass-dependent scatter, reionization-induced suppression of the halo occupation fraction, galaxy assembly bias, and alternative cosmologies. Combining with the results from Paper I, we find that central red galaxies dominate the low-mass regime. Our results motivate a hypothesis in which SFE is significantly higher than previously thought prior to reionization, enabling relatively massive galaxies to form in small haloes. These systems are subsequently quenched by the UV background, producing the central red dwarf galaxies observed. Finally, we obtain $3σ$ and $5σ$ upper mass bounds of $10^{8.80}\,h^{-1}{\rm M}_{\odot}$ and $10^{10.24}\,h^{-1}{\rm M}_{\odot}$ on the smallest haloes required to exist.

Xu, Kun [Pennsylvania U.; Durham U., ICC; Tsung-Da↗

Photometric Objects Around Cosmic Webs (PAC) Delineated in a Spectroscopic Survey. IV. High-precision Constraints on the Evolution of the Stellar–Halo Mass Relation at Redshift z < 0.7

Taking advantage of the Photometric objects Around Cosmic webs method developed in Paper I, we measure the excess surface density $\overline{n}$ 2 w p of the photometric objects around spectroscopic objects down to stellar masses 10 8.0 M ⊙ , 10 9.2 M ⊙ , and 10 9.8 M ⊙ in the redshift ranges of z s < 0.2, 0.2 < z s < 0.4, and 0.5 < z s < 0.7, respectively, using data from the DESI Legacy Imaging Surveys and spectroscopic samples from the Sloan Digital Sky Survey (i.e., the Main, LOWZ, and CMASS samples). We model the measured in an N-body simulation, using the abundance matching method, and we constrain the stellar–halo mass relations (SHMRs) in the three redshift ranges to percent levels. With the accurate modeling, we demonstrate that the stellar mass scatter for a given halo mass is nearly a constant, and that the empirical form of Behroozi et al. describes the SHMR better than the double-power-law form at low mass. Our SHMR accurately captures the downsizing of massive galaxies from z s = 0.7, while it also indicates that small galaxies are still growing faster than their host halos. The galaxy stellar mass functions (GSMFs) from our modeling are in perfect agreement with the model-independent measurements in Paper III, although the current work extends the GSMFs to a much smaller stellar mass. Based on the GSMFs and the SHMRs, we derive the stellar mass completeness and halo occupation distributions for the LOWZ and CMASS samples, which are useful for correctly interpreting their cosmological measurements, such as galaxy–galaxy lensing and redshift space distortion.

79 ASTRONOMY AND ASTROPHYSICS↗

Self-reported health impacts of do-it-yourself air cleaner use in a smoke-impacted community

Smoke exposure from wildfires or residential wood burning for heat is a public health problem for many communities. Do-It-Yourself (DIY) portable air cleaners (PACs) are promoted as affordable alternatives to commercial PACs, but evidence of their effect on health outcomes is limited. Pilot test an evaluation of the effect of DIY PAC usage on self-reported symptoms, and investigate barriers and facilitators of PAC use, among members of a tribal community that routinely experiences elevated concentrations of fine particulate matter (PM 2.5 ) from smoke. We conducted studies in Fall 2021 (“wildfire study”; N = 10) and Winter 2022 (“wood stove study”; N = 17). Each study included four sequential one-to-two-week phases: 1) initial, 2) DIY PAC usage ≥8 h/day, 3) commercial PAC usage ≥8 h/day, and 4) air sensor with visual display and optional PAC use. We continuously monitored PAC usage and indoor/outdoor PM 2.5 concentrations in homes. Concluding each phase, we conducted phone surveys about participants’ symptoms, perceptions, and behaviors. We analyzed symptoms associated with PAC usage and conducted an analysis of indoor PM 2.5 concentrations as a mediating pathway using mixed effects multivariate linear regression. We categorized perceptions related to PACs into barriers and facilitators of use. No association was observed between PAC usage and symptoms, and the mediation analysis did not indicate that small observed trends were attributable to changes in indoor PM 2.5 concentrations. Small sample sizes hindered the ability to draw conclusions regarding the presence or absence of causal associations. DIY PAC usage was low; loud operating noise was a barrier to use. This research is novel in studying health effects of DIY PACs during wildfire and wood smoke exposures. Such research is needed to inform public health guidance. Recommendations for future studies on PAC use during smoke exposure include building flexibility of intervention timing into the study design.

54 ENVIRONMENTAL SCIENCES↗

Assessing the use of portable air cleaners for reducing exposure to airborne diseases in a conference room with thermal stratification

The COVID-19 pandemic has highlighted the need for strategies that mitigate the risk of aerosol disease transmission in indoor environments with different ventilation strategies. It is necessary for building operators to be able to estimate and compare the relative impacts of different mitigation strategies to determine suitable strategies for a particular situation. Using a validated CFD model, this study simulates the dispersion of exhaled contaminants in a thermally stratified conference room with overhead heating. The impacts of portable air-cleaners (PACs) on the room airflow and contaminant distribution were evaluated for different PAC locations and flow rates, as well as for different room setups (socially distanced or fully occupied). To obtain a holistic view of a strategy's impacts under different release scenarios, we simultaneously model the steady-state distribution of aerosolized virus contaminants from eight distinct sources in 18 cases for a total of 144 release scenarios. The simulations show that the location of the source, the PAC settings, and the room set-up can impact the average exposure and PAC effectiveness. For this studied case, the PACs reduced the room average exposure by 31%-66% relative to the baseline case. Some occupant locations were shown to have a higher-than-average exposure, particularly those seated near the airflow outlet, and occupants closest to sources tended to see the highest exposure from said source. We found that these PACs were effective at reducing the stratification caused by overhead heating, and also identified at least one sub-optimal location for placing a PAC in this space.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Protection and enrichment: how two different carbonaceous biofilm supports improve methane yield from encapsulated anaerobic microorganisms

Encapsulating anaerobic microorganisms allows for the separation of the solids retention time from the hydraulic retention time during anaerobic wastewater treatment. The harsh chemistries involved in the process of encapsulation can have adverse effects on microorganisms for anaerobic digestion, especially methanogens, and can lead to lower methane yields after encapsulation. Improving the survival and maintaining activity of anaerobic communities during encapsulation will likely be the key to improving methane yield. In this study, we investigated the encapsulation of biomass grown as biofilms on two carbonaceous materials, biochar and powdered activated carbon (PAC), to improve methane yield. Microorganisms grown as biofilms on biochar and PAC were encapsulated in polyethylene glycol (PEG) and incubated for 10 days. After 10 days, the unamended control capsules produced 81.6 ± 5.4 μmol of methane, while PAC-amended capsules produced 129.8 ± 1.9 μmol and biochar-amended capsules produced 432.96 ± 20.8 μmol methane, with the differences being statistically significant (p < 0.05). In biochar, a higher relative abundance of methanogens led to increased methane production capacity. The ratio of the methyl coenzyme M reductase (mcrA) genes to total 16S rRNA genes in the encapsulated biochar-supported biofilms was significantly higher than that in the encapsulated unsupported (p = 4.9 × 10 −5 ) and the PAC-supported biofilms (p = 0.012). Biochar-supported biofilms also had higher methane output per mcrA or 16S rRNA gene copy number. For the PAC, biofilms were protected from ammonium persulfate (APS), a powerful oxidant used in the encapsulation process. PAC removed 92% of dissolved APS, reducing exposure of the methanogens to this chemical. Unfortunately, this removal of APS compromised capsule stability, limiting the amount of PAC that could be added to the capsules. Furthermore, amendments that improve survival and activity of methanogens should be used in the capsules instead of those that protect methanogens by interfering with encapsulant polymerization chemistry.

Resource recovery↗

Molecular determinants of pH sensing in the proton-activated chloride channel

In response to acidic pH, the widely expressed proton-activated chloride (PAC) channel opens and conducts anions across cellular membranes. By doing so, PAC plays an important role in both cellular physiology (endosome acidification) and diseases associated with tissue acidosis (acid-induced cell death). Despite the available structural information, how proton binding in the extracellular domain (ECD) leads to PAC channel opening remains largely unknown. Here, through comprehensive mutagenesis and electrophysiological studies, we identified several critical titratable residues, including two histidine residues (H130 and H131) and an aspartic acid residue (D269) at the distal end of the ECD, together with the previously characterized H98 at the transmembrane domain–ECD interface, as potential pH sensors for human PAC. Mutations of these residues resulted in significant changes in pH sensitivity. Some combined mutants also exhibited large basal PAC channel activities at neutral pH. By combining molecular dynamics simulations with structural and functional analysis, we further found that the β12 strand at the intersubunit interface and the associated “joint region” connecting the upper and lower ECDs allosterically regulate the proton-dependent PAC activation. Our studies suggest a distinct pH-sensing and gating mechanism of this new family of ion channels sensitive to acidic environment.

59 BASIC BIOLOGICAL SCIENCES↗

Cyclobutanedicarboxylate Metal–Organic Frameworks as a Platform for Dramatic Amplification of Pore Partition Effect

Ultrafine tuning of MOF structures at sub-angstrom or picometer levels can help improve separation selectivity for gases with subtle differences. However, for MOFs with large-enough pore size, the effect from ultrafine tuning on sorption can be muted. Here we show an integrative strategy that couples together extreme pore compression with ultrafine pore tuning. Furthermore, this strategy is made possible by unique combination of two features of the pacs platform (pacs = partitioned acs): multi-modular framework and exceptional tolerance towards isoreticular replacement. Specifically, we use one module (Ligand 1, L1) to shrink pore size to an extreme minimum on pacs. A compression ratio of about 30% was achieved (based on unit-cell c/a ratio) from prototypical 1,4-benzenedicarboxylate-pacs to trans-1,3-cyclobutanedicarboxylate-pacs. This is followed by using another module (Ligand 2, L2) for ultrafine pore tuning (< 3% compression). This L1-L2 strategy increases C 2 H 2 /CO 2 selectivity from 2.6 to 20.8 and gives rise to excellent experi-mental breakthrough performance. Being the shortest cyclic dicarboxylate that mimics para-benzene-based moieties us-ing bioisosteric (BIS) strategy on pacs, trans-1,3-cyclobutanedicarboxylate-based MOF chemistry offers new opportuni-ties in MOF chemistry.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Pore space partition of metal-organic frameworks for gas storage and separation

Pore space partition (PSP) concept is a synthetic design concept and can also serve as a structure analysis method useful for next-step synthetic planning and execution. PSP provides an integrated chemistry-topology-focused tool to design new materials platforms. While PSP is no less effective for making large-pore materials, the growing importance of small-molecule gas storage and separation for green-energy applications provides impetus for developing small-pore materials for which the PSP strategy is uniquely suited. Currently, the best embodiment of the PSP concept is the partitioned-acs (pacs) platform in which both fine or coarse adjustments to the building blocks have sparked a transformation of a prototype framework into a huge and continuously expanding family of chemically robust materials with controllable pore metrics and functionalities suitable for tailored applications. The pacs compositional diversity results from the platform’s intrinsic multi-module nature, geometric flexibility and tolerance towards individual module variations, and mutual structure-directing effects among various modules, all of which combine to enable the molecular-level uniform co-assemblies of chemical components rarely seen together elsewhere. Here, in this contribution, we present an overview of different pore space engineering methods and how different MOF materials have contributed to important advances in chemical stability, industrial gas storage and gas separation. In particular, we will focus on synthetic assembly of the pacs system, highlighting the differences of pacs materials from other MOF platforms and advantages of pacs materials in enhancing various MOF properties.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Experimental and Modeled Assessment of Interventions to Reduce PM2.5 in a Residence during a Wildfire Event

Increasingly large and frequent wildfires affect air quality even indoors by emitting and dispersing fine/ultrafine particulate matter known to pose health risks to residents. With this health threat, we are working to help the building science community develop simplified tools that may be used to estimate impacts to large numbers of homes based on high-level housing characteristics. In addition to reviewing literature sources, we performed an experiment to evaluate interventions to mitigate degraded indoor air quality. We instrumented one residence for one week during an extreme wildfire event in the Pacific Northwest. Outdoor ambient concentrations of PM2.5 reached historic levels, sustained at over 200 μg/m3 for multiple days. Outdoor and indoor PM2.5 were monitored, and data regarding building characteristics, infiltration, and mechanical system operation were gathered to be consistent with the type of information commonly known for residential energy models. Two conditions were studied: a high-capture minimum efficiency rated value (MERV 13) filter integrated into a central forced air (CFA) system, and a CFA with MERV 13 filtration operating with a portable air cleaner (PAC). With intermittent CFA operation and no PAC, indoor corrected concentrations of PM2.5 reached 280 μg/m3, and indoor/outdoor (I/O) ratios reached a mean of 0.55. The measured I/O ratio was reduced to a mean of 0.22 when both intermittent CFA and the PAC were in operation. Data gathered from the test home were used in a modeling exercise to assess expected I/O ratios from both interventions. The mean modeled I/O ratio for the CFA with an MERV 13 filter was 0.48, and 0.28 when the PAC was added. The model overpredicted the MERV 13 performance and underpredicted the CFA with an MERV 13 filter plus a PAC, though both conditions were predicted within 0.15 standard deviation. The results illustrate the ways that models can be used to estimate indoor PM2.5 concentrations in residences during extreme wildfire smoke events.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Multi‐Stage Optimization of Pore Size and Shape in Pore‐Space‐Partitioned Metal–Organic Frameworks for Highly Selective and Sensitive Benzene Capture

Abstract Compared to exploratory development of new structure types, pushing the limits of isoreticular synthesis on a high‐performance MOF platform may have higher probability of achieving targeted properties. Multi‐modular MOF platforms could offer even more opportunities by expanding the scope of isoreticular chemistry. However, navigating isoreticular chemistry towards best properties on a multi‐modular platform is challenging due to multiple interconnected pathways. Here on the multi‐modular pacs (partitioned acs) platform, we demonstrate accessibility to a new regime of pore geometry using two independently adjustable modules (framework‐forming module 1 and pore‐partitioning module 2). A series of new pacs materials have been made. Benzene/cyclohexane selectivity is tuned, progressively, from 4.5 to 15.6 to 195.4 and to 482.5 by pushing the boundary of the pacs platform towards the smallest modules known so far. The exceptional stability of these materials in retaining both porosity and single crystallinity enables single‐crystal diffraction studies of different crystal forms (as‐synthesized, activated, guest‐loaded) that help reveal the mechanistic aspects of adsorption in pacs materials.

Chen, Yichong↗

A Strategy for Constructing Pore-Space-Partitioned MOFs with High Uptake Capacity for C 2 Hydrocarbons and CO 2

Introduction of pore partition agents into hexagonal channels of MIL-88 type (acs topology) endows materials with high tunability in gas sorption. Here, we report a strategy to partition acs framework into pacs (partitioned acs) crystalline porous materials (CPM). This strategy is based on insertion of in situ synthesized 4, 4'-dipyridylsulfide (dps) ligands. As a result, one third of open metal sites in the parent acs net are retained in pacs MOFs, while two thirds are used for pore space partition. The newly synthesized Co 2 V-pacs MOFs, with optimized pore space and open metal sites, exhibit near or at record high uptake capacities for C 2 H 2 , C 2 H 4 , C 2 H 6 , and CO 2 among MOFs. For example, the storage capacity of C 2 H 2 is 234 cm 3 /g -1 (298 K) and 330 cm 3 /g -1 (273K) at 1 atm for CPM-733-dps (the Co 2 V-BDC form, BDC=1,4-benzenedicarboxylate), higher than benchmark MOFs such as MOF-74 and all other pacs members. These high uptake capacities are accomplished with low heat of adsorption, a feature desirable for low-energy-cost adsorbent regeneration. CPM-733-dps is stable and shows no loss of C 2 H 2 adsorption capacity following multiple adsorption–desorption cycles.

25 ENERGY STORAGE↗