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CuI is an important semiconductor with a transparency in the visible light range. However, the β phase structure at 643–673 K is controversial. We used density functional theory (DFT) combined with quasi-harmonic approximation (QHA) to investigate β-CuI. By analyzing the relative energy, elastic and vibrational properties, and finite-temperature free energy, we ruled out the previously proposed candidate structure (CS) with space group R3̅mand proposed a 2D bilayered stacking structure. DFT-QHA calculations showed that CSs with P3̅m1 and P3m1 space groups, which share the same 2D bilayer structure but differ in stacking, have lower free energies than γ-CuI above 310 K. Calculations of the transition pathways using the generalized solid-state nudged elastic band method indicate that the ZB to bilayered structure transformation requires an energy barrier of ∼100 meV/f.u. to overcome, while interlayer sliding needs only ∼20 meV/f.u.

This article presents the pulling mitigation scheme implemented in the frequency synthesizer integrated with the dual-band narrowband-internet-of-things (NB-IoT) transmitter (TX). The proposed pulling mitigation in the synthesizer employs a hybrid phase compensation and sampled filter to mitigate the pulling effects by the transmitter. The synthesizer covers frequencies from 700–900 MHz and 1.7–2 GHz in the low band and high band, respectively, satisfying the dual-band NB-IoT frequency tuning specifications. The proposed pulling mitigation in the synthesizer improves the error vector magnitude (EVM) by 11.5% with 16 quadrature amplitude modulation (QAM) modulation and in single-tone measurements, the achieved pulling suppression is 24 dB. Implemented in 40 nm CMOS, the pulling mitigation occupies a small area of $0.18\times0.18$ mm2 and the dc power consumption is 1 mW with a supply voltage of 1.1 V.

Metal halide perovskites (MHPs) have soft lattices with strong anharmonicity and will undergo entropy-driven solid–solid phase transitions upon heating. Here, we investigate the polymorph stabilities and phase transitions in one of the lead-free MHPs, CsSnI3, by several molecular simulation techniques. Three different phase transitions (γ ↔ β, β ↔ α, and yellow → black) in CsSnI3have been successfully reproduced by molecular dynamics (MD) simulations with a newly developed empirical force field. The heating and annealing MD simulations and free-energy calculations with the non-equilibrium thermodynamic integration (NETI) method predict the transition temperatures of 275, 385, and 280 K for the γ ↔ β, β ↔ α, and yellow → black transitions, respectively. Lattice dynamics (LD) simulations within the harmonic approximation fail to predict the correct phase stability in CsSnI3at high temperatures. The quasiharmonic approximation (QHA) calculations that include the volume dependence of the phonon frequencies and lattice energies correctly predict all phase transitions in CsSnI3. However, the transition temperatures of the γ ↔ β and β ↔ α transitions predicted by the QHA calculations significantly deviate from those by MD simulations. By comparing the Gibbs free energies calculated by the LD simulations within the QHA and MD-based NETI method, we find the differences of 3–30 meV for different polymorphs. Although calculations based on the harmonic model can provide valuable information, the anharmonic terms need to be included for accurate predictions of transition temperatures of phase transitions in CsSnI3and other MHPs.

Herbicides are critical resources for meeting agricultural demand. While similar in structure and function to pharmaceuticals, the development of new herbicidal mechanisms of action and new scaffolds against known mechanisms of action has been much slower than in pharmaceutical sciences. We hypothesized that this may be due in part to a relative undersampling of possible herbicidal chemistries and set out to test whether this difference in sampling existed and whether increasing the diversity of possible herbicidal chemistries would be likely to result in more efficacious herbicides. To conduct this work, we first identified databases of commercially available herbicides and clinically approved pharmaceuticals. Using these databases, we created a two-dimensional embedding of the chemical, which provides a qualitative visualization of the degree to which each chemotype is distributed within the combined chemical space and shows a moderate degree of overlap between the two sets. Next, we trained several machine learning models to classify herbicides versus drugs based on physicochemical characteristics. The most accurate of these models has an accuracy of 93% with the key differentiating characteristics being the number of polar hydrogens, number of amide bonds, LogP, and polar surface area. We then used several types of scaffold decomposition to quantitatively evaluate the chemical diversity of each molecular family and showed herbicides to have considerably fewer unique structural fragments. Finally, we used molecular docking as an in silicoevaluation of further structural diversification in herbicide development. To this end, we identified herbicides with well-characterized binding sites and modified those scaffolds based on similar structural subunits from the drug dataset not present in any commercial herbicide while using the machine-learned model to ensure that required herbicide properties were maintained. Redocking the original and modified scaffolds of several herbicides showed that even this simple design strategy is capable of yielding new molecules with higher predicted affinity for the target enzymes. Overall, we show that herbicides are distinct from drugs based on physicochemical properties but less diverse in their chemistry in a way not governed by these properties. We also demonstrate in silicothat increasing the diversity of herbicide scaffolds has the potential to increase potency, potentially reducing the amount needed in agricultural practice.

CA-125, the most frequently used biomarker for ovarian cancer detection, cannot provide accurate diagnosis due to its poor specificity as it may also increase in many benign gynecological conditions. Thus, reducing the false-positive outcomes is urgently needed. Decrease in terminal galactosylated N-glycans of serum IgG has been found in various malignancies compared to healthy controls. Here, this alteration of IgG galactosylation was extended to be investigated between ovarian cancer and benign conditions with similar elevated CA-125 levels, in an attempt to effectively distinguish between false-positive subjects and ovarian cancer patients. In the study of 58 patients with elevated CA-125 levels (>35 U/mL), the degree of IgG galactosylation was measured from the relative intensities of IgG digalactosyl (G2), monogalactosyl (G1), and agalactosylated (G0) N-glycans according to the formula G0/(G1 + G2·2). This ratio was found significantly higher in the malignant group than in the benign group (0.74 vs 0.34; p< 0.0001). ROC analysis demonstrated an improved specificity from 65.2% (by CA-125 test alone) to 84.6%, while maintaining sensitivity at 90% by incorporating quantitative analysis of IgG galactosylation in the current assay. The results suggest that combining quantitative alteration of IgG galactosylation with CA-125 may generate an overall more robust approach for differential diagnosis of ovarian cancer.

We and others have recently reported cloning and characterization of human prk and plk, members of the polo family of protein serine/threonine kinases that includes the budding yeast cdc5 and Drosophila melanoganster polo. The cdc5 gene is essential for cell cycle progression through mitosis and controls adaptation to the yeast DNA damage checkpoint. Here we report the identification of two new cdc5 homologs from Ceanovhabditis elegans, named plcl and plc2. The deduced amino acid sequences of Plcl and Plc2 share strong homology with both human Prk and Plk. plcl and plc2 genes are closely linked on chromosome III and share 40% residue identity, suggesting that gene duplication followed by independent evolution gives rise to multiple polo homologous genes within a species. Similar to polo family members in other species, two distinct domains are present in Plcl and Plc2 with the N-terminal half being the putative kinase domain. Interestingly, Plc2, unlike Plcl, contains a less conserved polo box within the C-terminal half of the protein, suggesting a functional division between these two kinases.

Activated macrophage-conditioned medium (M-CM) induces megakaryocytic differentiation of HIMeg-1 cells. The megakaryocytic differentiation activity (MDA) is proteinaceous since it is susceptible to treatments by proteinases, heat, and reducing agents. MDA is not thrombopoietin (TPO) since (1) TPO alone or in conjunction with several other recombinant cytokines fails to induce any degree of HIMeg-1 cell differentiation; and (2) a neutralizing antibody against TPO or an antibody against the extracellular domain of c-mplis unable to abolish M-CM-induced CD41 expression on HIMeg-1 cells. Reverse transcriptase-mediated polymerase chain reaction shows that HIMeg-1 cells express c-mplbut not TPO. Additional neutralizing antibody studies suggest that MDA is not one of the cytokines known to induce some degree of megakaryopoiesis in vitro or in vivo including interleukin 3 (IL-3), IL-6, IL-11, granulocyte–macrophage colony-stimulating factor, erythropoietin, or stem cell factor. On the other hand, MDA appears to be a combination of interferon γ (IFN-γ) and tumour necrosis factor α (TNF-α), since neutralizing antibodies against these two cytokines completely abolish MDA-induced CD41 expression. In addition, either recombinant human IFN-γ or TNF-α alone is capable of inducing CD41 and CD42 expression on HIMeg-1 cells. In combination, IFN-γ and TNF-α induce a maximal level of CD41 and CD42 expression which is also accompanied by an increase in cell size and DNA ploidy level. Thus, our studies indicate that IFN-γ/TNF-α is capable of inducing megakaryocytic differentiation of the HIMeg-1 cell line and that HIMeg-1 is a good system for studying the molecular mechanism mediating megakaryocytic differentiation.

We describe the mapping and sequencing of mutations within the DNA polymerase gene of herpes simplex virus type 1 which confer resistance to aphidicolin, a DNA polymerase inhibitor. The mutations occur near two regions which are highly conserved among DNA polymerases related to the herpes simplex enzyme. They also occur near other herpes simplex mutations which affect the interactions between the polymerase and deoxyribonucleoside triphosphate substrates. Consequently, we argue in favor of the idea that the aphidicolin binding site overlaps the substrate binding site and that the near-by conserved regions are functionally required for substrate binding. Our mutants also exhibit abnormal sensitivity to another DNA polymerase inhibitor, phosphonoacetic acid. This drug is thought to bind as an analogue of pyrophosphate. A second-site mutation which suppresses the hypersensitivity of one mutant to phosphonoacetic acid (but not its aphidicolin resistance) is described. This second mutation may represent a new class of mutations, which specifically affects pyrophosphate, but not substrate, binding.

Hepatocyte Nuclear Factor 4 (HNF-4), a liver-enriched orphan receptor of the nuclear receptor superfamlly, is required for the expression of a wide variety of liver-specific genes including apoAl. To explore the possibility that site A of the apoAl gene enhancer might also be the target for HNF-4 without the interference of endogenous mamalian cell proteins that also bind to site A, we tested the ability of HNF-4 to activate transcription from site A in yeast cells. Electrophoretlc mobility shift assays (EMSA) and Scatchard plot analysis demonstrated that yeast produced HNF-4 binds to site A with an affinity two times higher than that of yeast produced RXRa. Mapping analysis indicated that the 5' portion of site A containing two Imperfect direct repeats (TGAACCCTTGACC) and the sequence of the trinucleotide spacer (CCT) between these Imperfect repeats are critical determinants for selective binding and transactlvation by HNF-4. Similar observations were obtained when these mutated versions of site A were evaluated by transient cotransfection assays in CV1 cells. We conclude that the unique structural determinants of site A in conjunction with the differential binding affinity of HNF-4 for site A may play a fundamental role In apoAl gene regulation.