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1. Lower Bounds Against Sparse Symmetric Functions of ACC Circuits: Expanding the Reach of #SAT Algorithms

   https://doi.org/10.1007/s00224-022-10106-8  

   Vyas, Nikhil ; Williams, R. Ryan ( November 2022 , Theory of Computing Systems)

   We continue the program of proving circuit lower bounds via circuit satisfiability algorithms. So far, this program has yielded several concrete results, proving that functions in$\mathsf {Quasi}\text {-}\mathsf {NP} = \mathsf {NTIME}[n^{(\log n)^{O(1)}}]$$\mathrm{Quasi}-\mathrm{NP}=\mathrm{NTIME}\left[n^{{\left(\log n\right)}^{O\left(1\right)}}\right]$and other complexity classes do not have small circuits (in the worst case and/or on average) from various circuit classes$\mathcal { C}$$C$, by showing that$\mathcal { C}$$C$admits non-trivial satisfiability and/or#SAT algorithms which beat exhaustive search by a minor amount. In this paper, we present a new strong lower bound consequence of having a non-trivial#SAT algorithm for a circuit class${\mathcal C}$$C$. Say that a symmetric Boolean functionf(x₁,…,x_n) issparseif it outputs 1 onO(1) values of${\sum }_{i} x_{i}$${\sum }_i{x}_i$. We show that for every sparsef, and for all “typical”$\mathcal { C}$$C$, faster#SAT algorithms for$\mathcal { C}$$C$circuits imply lower bounds against the circuit class$f \circ \mathcal { C}$$f\circ C$, which may bestrongerthan$\mathcal { C}$$C$itself. In particular:

   #SAT algorithms forn^k-size$\mathcal { C}$$C$-circuits running in 2ⁿ/n^ktime (for allk) implyNEXPdoes not have$(f \circ \mathcal { C})$$(f\circ C)$-circuits of polynomial size.

   #SAT algorithms for$2^{n^{{\varepsilon }}}$$2^{n^{\epsilon }}$-size$\mathcal { C}$$C$-circuits running in$2^{n-n^{{\varepsilon }}}$$2^{n-n^{\epsilon }}$time (for someε> 0) implyQuasi-NPdoes not have$(f \circ \mathcal { C})$$(f\circ C)$-circuits of polynomial size.

   Applying#SAT algorithms from the literature, one immediate corollary of our results is thatQuasi-NPdoes not haveEMAJ∘ACC⁰∘THRcircuits of polynomialmore »size, whereEMAJis the “exact majority” function, improving previous lower bounds againstACC⁰[Williams JACM’14] andACC⁰∘THR[Williams STOC’14], [Murray-Williams STOC’18]. This is the first nontrivial lower bound against such a circuit class.

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2. Isoelectronic perturbations to f - d -electron hybridization and the enhancement of hidden order in URu ₂ Si ₂

   https://doi.org/10.1073/pnas.2026591118  

   Wolowiec, Christian T. ; Kanchanavatee, Noravee ; Huang, Kevin ; Ran, Sheng ; Breindel, Alexander J. ; Pouse, Naveen ; Sasmal, Kalyan ; Baumbach, Ryan E. ; Chappell, Greta ; Riseborough, Peter S. ; et al ( May 2021 , Proceedings of the National Academy of Sciences)

   Electrical resistivity measurements were performed on single crystals of URu_2–xOs_xSi₂up tox= 0.28 under hydrostatic pressure up toP= 2 GPa. As the Os concentration,x, is increased, 1) the lattice expands, creating an effective negative chemical pressureP_ch(x); 2) the hidden-order (HO) phase is enhanced and the system is driven toward a large-moment antiferromagnetic (LMAFM) phase; and 3) less external pressureP_cis required to induce the HO→LMAFM phase transition. We compare the behavior of theT(x,P) phase boundary reported here for the URu_2-xOs_xSi₂system with previous reports of enhanced HO in URu₂Si₂upon tuning withPor similarly in URu_2–xFe_xSi₂upon tuning with positiveP_ch(x). It is noteworthy that pressure, Fe substitution, and Os substitution are the only known perturbations that enhance the HO phase and induce the first-order transition to the LMAFM phase in URu₂Si₂. We present a scenario in which the application of pressure or the isoelectronic substitution of Fe and Os ions for Ru results in an increase in the hybridization of the U-5f-electron and transition metald-electron states which leads to electronic instability in the paramagnetic phase and the concurrent formation of HO (and LMAFM) in URu₂Si₂. Calculations in the tight-binding approximation are included to determine the strength of hybridization between the U-5f-electron states and thed-electron states ofmore »Ru and its isoelectronic Fe and Os substituents in URu₂Si₂.

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3. Temporal trends in molecular markers of drug resistance in Plasmodium falciparum in human blood and profiles of corresponding resistant markers in mosquito oocysts in Asembo, western Kenya

   https://doi.org/10.1186/s12936-022-04284-6  

   Zhou, Zhiyong ; Gimnig, John E. ; Sergent, Sheila B. ; Liu, Ying ; Abong’o, Bernard ; Otieno, Kephas ; Chebore, Winnie ; Shah, Monica P. ; Williamson, John ; ter Kuile, Feiko O. ; et al ( September 2022 , Malaria Journal)

   Over the last two decades, the scale-up of vector control and changes in the first-line anti-malarial, from chloroquine (CQ) to sulfadoxine-pyrimethamine (SP) and then to artemether-lumefantrine (AL), have resulted in significant decreases in malaria burden in western Kenya. This study evaluated the long-term effects of control interventions on molecular markers ofPlasmodium falciparumdrug resistance using parasites obtained from humans and mosquitoes at discrete time points.

   Dried blood spot samples collected in 2012 and 2017 community surveys in Asembo, Kenya were genotyped by Sanger sequencing for markers associated with resistance to SP (Pfdhfr, Pfdhps), CQ, AQ, lumefantrine (Pfcrt, Pfmdr1)and artemisinin (Pfk13).Temporal trends in the prevalence of these markers, including data from 2012 to 2017 as well as published data from 1996, 2001, 2007 from same area, were analysed. The same markers from mosquito oocysts collected in 2012 were compared with results from human blood samples.

   The prevalence of SPdhfr/dhpsquintuple mutant haplotype C₅₀I₅₁R₅₉N₁₀₈I₁₆₄/S₄₃₆G₄₃₇E₅₄₀A₅₈₁A₆₁₃increased from 19.7% in 1996 to 86.0% in 2012, while an increase in the sextuple mutant haplotype C₅₀I₅₁R₅₉N₁₀₈I₁₆₄/H₄₃₆G₄₃₇E₅₄₀A₅₈₁A₆₁₃containingPfdhps-436H was found from 10.5% in 2012 to 34.6% in 2017. ResistantPfcrt-76 T declined from 94.6% in 2007 to 18.3% in 2012 and 0.9% in 2017. MutantPfmdr1-86Y decreased across years from 74.8% in 1996 tomore »zero in 2017, mutantPfmdr1-184F and wildPfmdr1-D1246 increased from 17.9% to 58.9% in 2007 to 55.9% and 90.1% in 2017, respectively.Pfmdr1haplotype N₈₆F₁₈₄S₁₀₃₄N₁₀₄₂D₁₂₄₆ increased from 11.0% in 2007 to 49.6% in 2017. No resistant mutations inPfk13were found. Prevalence ofPfdhps-436H was lower while prevalence ofPfcrt-76 T was higher in mosquitoes than in human blood samples.

   This study showed an increased prevalence ofdhfr/dhpsresistant markers over 20 years with the emergenceof Pfdhps-436H mutant a decade ago in Asembo. The reversal ofPfcrtfrom CQ-resistant to CQ-sensitive genotype occurred following 19 years of CQ withdrawal. NoPfk13markers associated with artemisinin resistance were detected, but the increased haplotype ofPfmdr1N₈₆F₁₈₄S₁₀₃₄N₁₀₄₂D₁₂₄₆was observed. The differences in prevalence ofPfdhps-436H andPfcrt-76 T SNPs between two hosts and the role of mosquitoes in the transmission of drug resistant parasites require further investigation.

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4. Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases

   https://doi.org/10.1186/s12920-021-01126-3  

   McGuire Sams, Cierla ; Shepp, Kasey ; Pugh, Jada ; Bishop, Madison R. ; Merner, Nancy D. ( December 2021 , BMC Medical Genomics)

   Three genes clustered together on chromosome 12 comprise a group of hydroxycarboxylic acid receptors (HCARs):HCAR1,HCAR2, andHCAR3. These paralogous genes encode different G-protein coupled receptors responsible for detecting glycolytic metabolites and controlling fatty acid oxidation. Though better known for regulating lipid metabolism in adipocytes, more recently, HCARs have been functionally associated with breast cancer proliferation/survival;HCAR2has been described as a tumor suppressor andHCAR1andHCAR3as oncogenes. Thus, we sought to identify germline variants inHCAR1,HCAR2,andHCAR3that could potentially be associated with breast cancer risk.

   Two different cohorts of breast cancer cases were investigated, the Alabama Hereditary Cancer Cohort and The Cancer Genome Atlas, which were analyzed through nested PCRs/Sanger sequencing and whole-exome sequencing, respectively. All datasets were screened for rare, non-synonymous coding variants.

   Variants were identified in both breast cancer cohorts, some of which appeared to be associated with breast cancer BC risk, includingHCAR1c.58C > G (p.P20A),HCAR2c.424C > T (p.R142W),HCAR2c.517_518delinsAC (p.G173T),HCAR2c.1036A > G (p.M346V),HCAR2c.1086_1090del (p.P363Nfs*26),HCAR3c.560G > A (p.R187Q), andHCAR3c.1117delC (p.Q373Kfs*82). Additionally,HCAR2c.515C > T (p.S172L), a previously identified loss-of-function variant, was identified.

   Due to the important role of HCARs in breast cancer, it is vital to understand how these genetic variants play a role in breast cancer risk and proliferation and their consequences on treatment strategies. Additional studies will be needed to validate these findings. Nevertheless,more »the identification of these potentially pathogenic variants supports the need to investigate their functional consequences.

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5. TESS-Keck Survey. XIV. Two Giant Exoplanets from the Distant Giants Survey

   https://doi.org/10.3847/1538-3881/aca6ef  

   Van Zandt, Judah ; Petigura, Erik A. ; MacDougall, Mason ; Gilbert, Gregory J. ; Lubin, Jack ; Barclay, Thomas ; Batalha, Natalie M. ; Crossfield, Ian J. M. ; Dressing, Courtney ; Fulton, Benjamin ; et al ( January 2023 , The Astronomical Journal)

   We present the Distant Giants Survey, a three-year radial velocity campaign to measure P(DG∣CS), the conditional occurrence of distant giant planets (DG;M_p∼ 0.3–13M_J,P> 1 yr) in systems hosting a close-in small planet (CS;R_p< 10R_⊕). For the past two years, we have monitored 47 Sun-like stars hosting small transiting planets detected by TESS. We present the selection criteria used to assemble our sample and report the discovery of two distant giant planets, TOI-1669 b and TOI-1694 c. For TOI-1669 b we find that$M\sin i=0.573\pm 0.074M_{\mathrm{J}}$,P= 502 ± 16 days, ande< 0.27, while for TOI-1694 c,$M\sin i=1.05\pm 0.05M_{\mathrm{J}}$,P= 389.2 ± 3.9 days, ande= 0.18 ± 0.05. We also confirmed the 3.8 days transiting planet TOI-1694 b by measuring a true mass ofM= 26.1 ± 2.2M_⊕. At the end of the Distant Giants Survey, we will incorporate TOI-1669 b and TOI-1694 c into our calculation of P(DG∣CS), a crucial statistic for understanding the relationship between outer giants and small inner companions.