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The charge carriers of single-junction solar cells can be fluently extracted and then collected by electrodes, leading to weak charge carrier accumulation and low energy loss (E

Dopant-free organic hole transport materials (HTMs) remain highly desirable for stable and efficient n-i-p perovskite solar cells (pero-SCs) but rarely succeed. Here, we propose a molecular assembly strategy to overcome the limited optoelectronic properties of organic HTMs by precisely designing a linear organic small molecule BDT-DPA-F from the atomic to the molecular levels. BDT-DPA-F can assemble into a fibril network, showing an obviously improved hole mobility and decreased energy disorder. The resultant pero-SCs showed a promising efficiency of 23.12 % (certified 22.48 %), which is the highest certified value of pero-SCs with dopant-free HTMs, to date. These devices also showed a weak-dependence of efficiency on size, enabling a state-of-the-art efficiency of 22.50 % for 1-cm

Proteogenomics is an increasingly common method for species identification as it allows for rapid and inexpensive interrogation of an unknown organism’s proteome—even when the proteome is partially degraded. The proteomic method typically uses tandem mass spectrometry to survey all peptides detectable in a sample that frequently contains hundreds or thousands of proteins. Species identification is based on detection of a small numbers of species-specific peptides. Genetic analysis of proteins by mass spectrometry, however, is a developing field, and the bone proteome, typically consisting of only two proteins, pushes the limits of this technology. Nearly 20% of highly confident spectra from modern human bone samples identify non-human species when searched against a vertebrate database—as would be necessary with a fragment of unknown bone. These non-human peptides are often the result of current limitations in mass spectrometry or algorithm interpretation errors. Consequently, it is difficult to know if a “species-specific” peptide used to identify a sample is actually present in that sample. Here we evaluate the causes of peptide sequence errors and propose an unbiased, probabilistic approach to determine the likelihood that a species is correctly identified from bone without relying on species-specific peptides.

Perovskite solar cells (pero-SCs) performance is essentially limited by severe non-radiative losses and ion migration. Although numerous strategies have been proposed, challenges remain in the basic understanding of their origins. Here, we report a dielectric-screening-enhancement effect for perovskite defects by using organic semiconductors with finely tuned molecular structures from the atoms level. Our method produced various perovskite films with high dielectric constant values, reduced charge capture regions, suppressed ion migration, and it provides an efficient charge transport pathway for suppressing non-radiative recombination beyond the passivation effect. The resulting pero-SCs showed a promising power conversion efficiency (PCE) of 23.35% with a high open-circuit voltage (1.22 V); and the 1-cm

Organic materials with excitation wavelength-dependent (Ex-de) emission are highly attractive for anticounterfeiting, optoelectronics and bioassay applications; however, the realization of Ex-de fluorescence, independent of aggregation states, remains a challenge. We herein report a photoinduced electron transfer (PeT) strategy to design Ex-de fluorescence materials by manipulating the relaxation pathways of multiple excited states. As expected, the o-carborane dyad presents a clear Ex-de fluorescence colour in the aggregated states, resulting from the tunable relative intensity of the dual-fluorescence spectra. Taking TP[1]B as an example, the amorphous powders emitted bright blue-violet, white and yellow colours under 390 nm, 365 nm and 254 nm UV illumination, respectively. Importantly, multicolour, flexible and transparent films as well as an anticounterfeiting application using this o-carborane dyad are demonstrated.

Excitation wavelength dependent (Ex-De) emission materials have potential applications in anti-counterfeiting labels and bioimaging. Nevertheless, few purely organic chromophores are used in these areas. In this study, multiple excited states were incorporated into a molecule that was excited state intramolecular proton transfer (ESIPT) active, with the goal of manipulating the relaxation pathways of the excited states. The triazole derivative exhibits Ex-De photoluminescence (PL), and the maximum PL wavelength is located at 526 nm and 593 nm under a series of excitation wavelengths. Spectral identification indicates that the excimer and ESIPT processes are responsible for the green (526 nm) and orange (593 nm) fluorescence, respectively. Importantly, the quick response code and test strip prepared with this triazole derivative can be used for anti-counterfeiting and food spoilage detection applications, respectively. This research opens the door for developing novel Ex-De materials for anti-counterfeiting purposes.

In recent years, the intensified influences of global climate change and human activities have increased the frequency of large-scale debris flow disasters. As a result, main river channels often become blocked, thus forming a disaster chain of rivers dammed by debris flow followed by outburst flooding. In order to quickly and easily reveal the dynamic process of a debris flow dam breach, and quantitatively predict the outburst flood hazard, this study takes the Zhouqu “8.8” debris flow barrier dam in Western China as an example. Based on a stability assessment, China Institute of Water Resources and Hydropower Research ‘s Dam Breach Slope (DBS-IWHR), China Institute of Water Resources and Hydropower Research’s Dam Breach (DB-IWHR), and Hydrologic Engineering Center's River Analysis System (HEC-RAS) were integrated to simulate the development of dam breach, breach flood, and outburst flood evolution, respectively, under different scenarios. The simulated peak discharge flow of the actual spillway was 317.15 m3/s, which was consistent with the actual discharge of 316 m3/s. The results under different scenarios showed that, with the increased inflow of the barrier lake, the erosion rate of the dam increased, the peak discharge of the dam break flood increased, the peak arrival time shortened, and the downstream flooding area increased. These findings could provide scientific support for risk management and emergency decision-making with respect to barrier dam failure.

The built-in electric field (BEF) intensity of silicon heterojunction solar cells can be easily enhanced by selective doping to obtain high power conversion efficiencies (PCEs), while it is challenging for perovskite solar cells (pero-SCs) because of the difficulty in doping perovskites in a controllable way. Herein, an effective method is reported to enhance the BEF of FA

Many piezochromic luminescent (PCL) dyes are known for their fluorescent switching capacity in the powdered phase, but they are usually difficult to utilize practically owing to poor mechanical properties. Herein, a nanofiber film fabricated through an electrospinning process is doped with PCL dye. The electrospun film not only reveals the mechanics of macromolecular materials, but also achieves precise, gradient pressure recognition (ratiometric PCL behavior). The PCL sensitivity and color difference of the dye in a crystalline state are calculated to be 15.7 nm GPa-1 and 149 nm, respectively. The sensitivity of an electrospun film containing 0.1 % (w/w) dye decreased to 3.6 nm GPa-1 . Moreover, the individual effects of molecular conformation and intermolecular interaction on the PCL properties have been clearly distinguished through in situ high-pressure experiments. Intermolecular interactions play a more significant role in PCL color difference and sensitivity. The film fabricated through an electrospinning process contributes to understanding of the working mechanism and real applications of piezochromic materials.

The detection and sensing of acidic gases by optical sensors are of great importance in the fields of chemistry, environment and related industrial process. However, stretchable, low-cost, and tailorable sensors with high sensitivity and fast response remain a great challenge. In this work, we report a twisting donor–acceptor fluorophore (DBPA) with a hybridized local and charge-transfer excited state (HLCT) can serve as a visible dual-channel (colorimetric and fluorometric) sensor towards acid gas detection. Combination of the locally excited (LE) state and the high sensitive charge-transfer (CT) state, DBPA in aggregated state presents a high PL efficiency (ηPL > 76%), which exhibits over 98% PL quenching and a clear color difference (ΔE over 20) upon exposure to HCl gas. By incorporation of HLCT-active DBPA molecule into an elastomer host through an electrospinning process, new flexible and stretchable nanofiber films (SNMs) were prepared. Compared to non-porous rigid films, the sensitivity and response time of SNMs were obviously improved due to their large surface area and high porosity. It can be expected that, by taking the advantages of easy mass-production and low cost, such SNMs could be a promising optical material for practical sensory application.

Menstruation is the expulsion of the endometrial lining of the uterus following a nearly month long preparation for embryo implantation and pregnancy. Increasingly, the health of the endometrium is being recognized as a critical factor in female fertility, and proteomes and transcriptomes from endometrial biopsies at different stages of the menstrual cycle have been studied for both diagnostic and therapeutic purposes (1 Kao, L. C., et al. 2003 Endocrinology 144, 2870-2881; Strowitzki, Tet al. 2006 Hum. Reprod. Update 12, 617-630; DeSouza, L., et al. 2005 Proteomics 5, 270-281). Disorders of the uterus ranging from benign to malignant tumors, as well as endometriosis, can cause abnormal menstrual bleeding and are frequently diagnosed through endometrial biopsy (Strowitzki, Tet al. 2006 Hum. Reprod. Update 12, 617-630; Ferenczy, A. 2003 Maturitas 45, 1-14). Yet the proteome of menstrual blood, an easily available noninvasive source of endometrial tissue, has yet to be examined for possible causes or diagnoses of infertility or endometrial pathology. This study employed five different methods to define the menstrual blood proteome. A total of 1061 proteins were identified, 361 were found by at least two methods and 678 were identified by at least two peptides. When the menstrual blood proteome was compared with those of circulating blood (1774 proteins) and vaginal fluid (823 proteins), 385 proteins were found unique to menstrual blood. Gene ontology analysis and evaluation of these specific menstrual blood proteins identified pathways consistent with the processes of the normal endometrial cycle. Several of the proteins unique to menstrual blood suggest that extramedullary uterine hematopoiesis or parenchymal hemoglobin synthesis may be occurring in late endometrial tissue. The establishment of a normal menstrual blood proteome is necessary for the evaluation of its usefulness as a diagnostic tool for infertility and uterine pathologies. Identification of unique menstrual blood proteins should aid the forensic community in distinguishing menstrual blood from circulating blood.

RIG-I (retinoic acid-inducible gene I) and TRIM25 (tripartite motif protein 25) have emerged as key regulatory factors to induce interferon (IFN)-mediated innate immune responses to limit viral replication. Upon recognition of viral RNA, TRIM25 E3 ligase binds the first caspase recruitment domain (CARD) of RIG-I and subsequently induces lysine 172 ubiquitination of the second CARD of RIG-I, which is essential for the interaction with downstream MAVS/IPS-1/CARDIF/VISA and, thereby, IFN-beta mRNA production. Although ubiquitination has emerged as a major factor involved in RIG-I activation, the potential contribution of other post-translational modifications, such as phosphorylation, to the regulation of RIG-I activity has not been addressed. Here, we report the identification of serine 8 phosphorylation at the first CARD of RIG-I as a negative regulatory mechanism of RIG-I-mediated IFN-beta production. Immunoblot analysis with a phosphospecific antibody showed that RIG-I serine 8 phosphorylation steady-state levels were decreased upon stimulation of cells with IFN-beta or virus infection. Substitution of serine 8 in the CARD RIG-I functional domain with phosphomimetic aspartate or glutamate results in decreased TRIM25 binding, RIG-I ubiquitination, MAVS binding, and downstream signaling. Finally, sequence comparison reveals that only primate species carry serine 8, whereas other animal species carry an asparagine, indicating that serine 8 phosphorylation may represent a primate-specific regulation of RIG-I activation. Collectively, these data suggest that the phosphorylation of RIG-I serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction, further underscoring the importance of RIG-I and TRIM25 connection in type I IFN signal transduction.

Phosphorylation of the Kir3 channel by cAMP-dependent protein kinase (PKA) potentiates activity and strengthens channel-PIP(2) interactions, whereas phosphorylation by protein kinase C (PKC) exerts the opposite effects (Keselman et al., Channels 1:113-123, 2007; Lopes et al., Channels 1:124-134, 2007). Unequivocal identification of phosphorylated residues in ion channel proteins has been difficult, but recent advances in mass spectrometry techniques have allowed precise identification of phosphorylation sites (Park et al., Science 313:976-979, 2006). In this study, we utilized mass spectrometry to identify phosphorylation sites within the Kir3.1 channel subunit. We focused on the Kir3.1 C-terminal cytosolic domain that has been reported to be regulated by several modulators. In vitro phosphorylation by PKA exhibited a convincing signal upon treatment with a phosphoprotein stain. The phosphorylated C terminus was subjected to mass spectrometric analysis using matrix-assisted lased desorption/ionization-time of flight mass spectroscopy (MS). Peptides whose mass underwent a shift corresponding to addition of a phosphate group were then subjected to tandem MS (MS/MS) in order to confirm the modification and determine its precise location. Using this approach, we identified S385 as an in vitro phosphorylation site. Mutation of this residue to alanine resulted in a reduced sensitivity of Kir3.1* currents to H89 and Forskolin, confirming an in vivo role for this novel site of the Kir3.1 channel subunit in its regulation by PKA.

The objective of this study was to test the activity of microbicides against herpes simplex virus type 2 (HSV-2) introduced in seminal plasma. We found that seminal plasma interfered with the activity of PRO 2000 and of cellulose sulfate, increasing by 100-fold the concentration of drug required to inhibit 90% of viral plaque formation. Seminal plasma competitively inhibited binding of the microbicides to the HSV-2 envelope. Most of the interference was found in a high molecular-weight fraction; tandem mass spectrometry identified the proteins as fibronectin-1 and lactoferrin. In a murine model, the interference translated in vivo into a loss in protection. We found that 2% PRO 2000 gel protected 100% of mice challenged intravaginally with HSV-2 introduced in PBS, whereas only 55% of mice were protected if virus was introduced in seminal plasma (P=.0007, log rank test). If these findings are reflective of what occurs in humans, modifications to microbicides to ensure that they retain activity in the presence of seminal plasma are indicated.

Protein tyrosine phosphatases (PTPs) consist of a large family of enzymes known to play important roles in controlling virtually all aspects of cellular processes. However, assigning functional significance of PTPs in normal physiology and in diseases remains a major challenge in cell signaling. Since the function of a PTP is directly associated with its intrinsic activity, which is subject to post-translational regulation, new tools are needed to monitor the dynamic activities of PTPs, rather than mere abundance, on a global scale within the physiologically relevant environment of cells. To meet this objective, we report the synthesis and characterization of two rhodamine-conjugated probes that covalently label the active site of the PTPs in an activity-dependent manner, thus providing a direct readout of PTP activity and superior sensitivity, robustness, and quantifiability to previously reported biotinylated probes. We present evidence that the fluorescent probes can be used to identify new PTP markers and targets for potential diagnosis and treatment of human diseases. We also show that the fluorescent probes are capable of monitoring H(2)O(2)-mediated PTP inactivation, which should facilitate the study of regulated H(2)O(2) production as a new tier of control over tyrosine phosphorylation-dependent signal transduction. The ability to profile the entire PTP family on the basis of changes in their activity is expected to yield new functional insights into pathways regulated by PTPs and contribute to the discovery of PTPs as novel therapeutic targets.

Standard methods for body fluid identification typically rely on detection of the functional proteins specific to or enriched in them, such as hemoglobin in blood, alkaline phosphatase and PSA in semen, or α-amylase in saliva. While these markers can be relatively specific, the multiple methods used to identify them frequently rely on nonspecific chemical, enzymatic, or antibody reactions that usually require the structural integrity of the markers and are not confirmatory because other proteins or substances can also give positive test results. Recent advances in proteomics and mass spectrometry offer the ability to simultaneously detect multiple body fluid protein markers in a single, confirmatory test. Here, multiple markers for blood, saliva, and semen are identified by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Data demonstrate the ability to detect these body fluids at nanoliter to subnanoliter levels and to distinguish mixtures. Protein stability of mock samples assayed after 16 months showed no diminution of signal. Because multiple peptides from multiple protein markers are detected and effectively sequenced by MALDI MS/MS, the assay is confirmatory. As mass spectrometry detects whatever peptides are present in a sample, no a priori knowledge of an unknown stain is necessary to perform the test.

Previously, we have shown that statistical synergism between amino acid variants in thyroglobulin (Tg) and specific HLA-DR3 pocket sequence signatures conferred a high risk for autoimmune thyroid disease (AITD). Therefore, we hypothesized that this statistical synergism mirrors a biochemical interaction between Tg peptides and HLA-DR3, which is key to the pathoetiology of AITD. To test this hypothesis, we designed a recombinant HLA-DR3 expression system that was used to express HLA-DR molecules harboring either AITD susceptibility or resistance DR pocket sequences. Next, we biochemically generated the potential Tg peptidic repertoire available to HLA-DR3 by separately treating 20 purified human thyroglobulin samples with cathepsins B, D, or L, lysosomal proteases that are involved in antigen processing and thyroid biology. Sequences of the cathepsin-generated peptides were then determined by matrix-assisted laser desorption ionization time-of-flight-mass spectroscopy, and algorithmic means were employed to identify putative AITD-susceptible HLA-DR3 binders. From four predicted peptides, we identified two novel peptides that bound strongly and specifically to both recombinant AITD-susceptible HLA-DR3 protein and HLA-DR3 molecules expressed on stably transfected cells. Intriguingly, the HLA-DR3-binding peptides we identified had a marked preference for the AITD-susceptibility DR signatures and not to those signatures that were AITD-protective. Structural analyses demonstrated the profound influence that the pocket signatures have on the interaction of HLA-DR molecules with Tg peptides. Our study suggests that interactions between Tg and discrete HLA-DR pocket signatures contribute to the initiation of AITD.

L-Arginine deiminase from Pseudomonas aeruginosa (PaADI) catalyzes the hydrolysis of arginine to citrulline and ammonia. PaADI belongs to the guanidino group-modifying enzyme superfamily (GMSF), which conserves backbone fold and a Cys-, His-, and Asp-based catalytic core. In this paper the contributions made by the PaADI core residues Cys406, His278, and Asp166 and the contribution from the neighboring Asp280 (conserved in most but not all GMSF members) to catalysis of the formation and hydrolysis of the Cys406-alkyluronium intermediate were accessed by kinetic analysis of site-directed mutants. In addition, solution hydrolysis in a chemical model of the S-alkylthiouronium intermediate was examined to reveal the importance of general base catalysis in the enzymatic reaction. Substitutions of the active site gating residue Arg401, the l-arginine C(alpha)NH(3)(+)(COO(-)) binding residues, Arg185, Arg243, and Asn160, or the His278 hydrogen bond partner, Glu224, were found to cause dramatic reductions in the enzyme turnover rate. These results are interpreted to suggest that electrostatic interactions play a dominant role in PaADI catalysis. Structural variations observed in P. aeruginosa GMSF enzymes PaADI, agmatine deiminase (PaAgDI), and N(omega),N(omega)-dimethylarginine dimethylaminohydrolase (PaDDAH) indicate an early divergence of the encoding genes. Arginine analogues that are known substrates for PaAgDI and PaDDAH were tested with PaADI to define clear boundaries of biochemical function in the three hydrolases. The conservation of a catalytic core associated with the common chemical function and the divergence of substrate-binding residues (as well as one key catalytic residue) to expand the substrate range provide insight into the evolution of the catalysts that form the GMSF.

The PRL (phosphatase of regenerating liver) phosphatases constitute a novel class of small, prenylated phosphatases that are implicated in promoting cell growth, differentiation, and tumor invasion, and represent attractive targets for anticancer therapy. Here we describe the crystal structures of native PRL-1 as well as the catalytically inactive mutant PRL-1/C104S in complex with sulfate. PRL-1 exists as a trimer in the crystalline state, burying 1140 A2 of accessible surface area at each dimer interface. Trimerization creates a large, bipartite membrane-binding surface in which the exposed C-terminal basic residues could cooperate with the adjacent prenylation group to anchor PRL-1 on the acidic inner membrane. Structural and kinetic analyses place PRL-1 in the family of dual specificity phopsphatases with closest structural similarity to the Cdc14 phosphatase and provide a molecular basis for catalytic activation of the PRL phosphatases. Finally, native PRL-1 is crystallized in an oxidized form in which a disulfide is formed between the active site Cys104 and a neighboring residue Cys49, which blocks both substrate binding and catalysis. Biochemical studies in solution and in the cell support a potential regulatory role of this intramolecular disulfide bond formation in response to reactive oxygen species such as H2O2.