Iodonium Initiators: Paving the Air-free Oxidation of Spiro-OMeTAD for Efficient and Stable Perovskite Solar Cells.

To date, perovskite solar cells (pero-SCs) with doped 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (Spiro-OMeTAD) hole transporting layers (HTLs) have shown the highest recorded power conversion efficiencies (PCEs). However, their commercialization is still impeded by poor device stability owing to the hygroscopic lithium bis(trifluoromethanesulfonyl)imide and volatile 4-tert-butylpyridine dopants as well as time-consuming oxidation in air. In this study, we explored a series of single-component iodonium initiators with strong oxidability and different electron delocalization properties to precisely manipulate the oxidation states of Spiro-OMeTAD without air assistance, and the oxidation mechanism was clearly understood. Iodine (III) in the diphenyliodonium cation (IP+ ) can accept a single electron from Spiro-OMeTAD and forms Spiro-OMeTAD⋅+ owing to its strong oxidability. Moreover, because of the coordination of the strongly delocalized TFSI- with Spiro-OMeTAD⋅+ in a stable radical complex, the resulting hole mobility was 30 times higher than that of pristine Spiro-OMeTAD. In addition, the IP-TFSI initiator facilitated the growth of a homogeneous and pinhole-free Spiro-OMeTAD film. The pero-SCs based on this oxidizing HTL showed excellent efficiencies of 25.16 % (certified: 24.85 % for 0.062-cm2 ) and 20.71 % for a 15.03-cm2 module as well as remarkable overall stability.

Perovskite Grain-Boundary Manipulation Using Room-Temperature Dynamic Self-Healing "Ligaments" for Developing Highly Stable Flexible Perovskite Solar Cells with 23.8% Efficiency.

Flexible perovskite solar cells (pero-SCs) are the best candidates to complement traditional silicon SCs in portable power applications. However, their mechanical, operational, and ambient stabilities are still unable to meet the practical demands because of the natural brittleness, residual tensile strain, and high defect density along the perovskite grain boundaries. To overcome these issues, a cross-linkable monomer TA-NI with dynamic covalent disulfide bonds, H-bonds, and ammonium is carefully developed. The cross-linking acts as "ligaments" attached on the perovskite grain boundaries. These "ligaments" consisting of elastomers and 1D perovskites can not only passivate the grain boundaries and enhance moisture resistance but also release the residual tensile strain and mechanical stress in 3D perovskite films. More importantly, the elastomer can repair bending-induced mechanical cracks in the perovskite film because of dynamic self-healing characteristics. The resultant flexible pero-SCs exhibit promising improvements in efficiency, and record values (23.84% and 21.66%) are obtained for 0.062 and 1.004 cm2  devices; the flexible devices also show overall improved stabilities with T90  >20 000 bending cycles, operational stability with T90  >1248 h, and ambient stability (relative humidity = 30%) with T90  >3000 h. This strategy paves a new way for the industrial-scale development of high-performance flexible pero-SCs.

Functional Ionic Liquid Polymer Stabilizer for High-Performance Perovskite Photovoltaics.

The stability-related issues arising from the perovskite precursor inks, films, device structures and interdependence remain severely under-explored to date. Herein, we designed an ionic-liquid polymer (poly[Se-MI][BF4 ]), containing functional moieties like carbonyl (C=O), selenium (Se+ ), and tetrafluoroborate (BF4 - ) ions, to stabilize the whole device fabrication process. The C=O and Se+ can coordinate with lead and iodine (I- ) ions to stabilize lead polyhalide colloids and the compositions of the perovskite precursor inks for over two months. The Se+ anchored on grain boundaries and the defects passivated by BF4 - efficiently suppress the dissociation and migration of I- in perovskite films. Benefiting from the synergistic effects of poly[Se-MI][BF4 ], high efficiencies of 25.10 % and 20.85 % were exhibited by a 0.062-cm2 device and 15.39-cm2 module, respectively. The devices retained over 90 % of their initial efficiency under operation for 2200 h.

Regulating Charge Carrier Recombination in the Interconnecting Layer to Boost the Efficiency and Stability of Monolithic Perovskite/Organic Tandem Solar Cells.

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 (Eloss ). However, in tandem solar cells (TSCs), it is a considerable challenge to obtain a balance between the densities of the holes and electrons extracted from the two respective subcells to facilitate an efficient recombination in the interconnecting layer (ICL). Herein, a charge-carrier-dynamic management strategy for inorganic perovskite/organic TSCs is proposed, centered on the simultaneous regulation of the defect states of CsPbI1.9 Br1.1 perovskite in the front subcell and hole transport ability from the perovskite to ICL. The target hole density on the perovskite surface and the hole loss before reaching the ICL are significantly improved. As a result, the hole/electron density offset in the ICL can be effectively narrowed, leading to a balanced charge carrier recombination, which reduces the Eloss in TSCs. The resulting inorganic perovskite/organic 0.062-cm2 TSC exhibits a remarkable power conversion efficiency (PCE) of 23.17% with an ultrahigh open-circuit voltage (Voc ) of 2.15 V, and the PCE of the 1.004-cm2 device (21.69%) exhibited a weak size-dependence. This charge-carrier-dynamic management strategy can also effectively enhance the operational and ultraviolet-light stabilities of the TSCs.

Organic-semiconductor-assisted dielectric screening effect for stable and efficient perovskite solar cells.

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-cm2 pero-SCs maintained an excellent PCE (21.93%), showing feasibility for scalable fabrication. The robust operational and thermal stabilities revealed that this method paved a new way to understand the degradation mechanism of pero-SCs, promoting the efficiency, stability and scaled fabrication of the pero-SCs.

Molecular Self-Assembly Regulated Dopant-Free Hole Transport Materials for Efficient and Stable n-i-p Perovskite Solar Cells and Scalable Modules.

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-cm2 device and 20.17 % for 15.64-cm2 module. For the first time, the pero-SCs based on dopant-free HTMs realized ultralong stabilities with T80 lifetimes over 1200 h under operation or thermal aging at 85 °C.

Proteins, possibly human, found in World War II concentration camp artifact.

Museums displaying artifacts of the human struggle against oppression are often caught in their own internal struggle between presenting factual and unbiased descriptions of their collections, or relying on testament of survivors. Often this quandary is resolved in favor of what can be verified, not what is remembered. However, with improving instrumentation, methods and informatic approaches, science can help uncover evidence able to reconcile memory and facts. Following World War II, thousands of small, cement-like disks with numbers impressed on one side were found at concentration camps throughout Europe. Survivors claimed these disks were made of human cremains; museums erred on the side of caution-without documentation of the claims, was it justifiable to present them as fact? The ability to detect species relevant biological material in these disks could help resolve this question. Proteomic mass spectrometry of five disks revealed all contained proteins, including collagens and hemoglobins, suggesting they were made, at least in part, of animal remains. A new protein/informatics approach to species identification showed that while human was not always identified as the top contributor, human was the most likely explanation for one disk. To our knowledge, this is the first demonstration of protein recovery from cremains. Data are available via ProteomeXchange with identifier PXD035267.

High-Polarizability Organic Ferroelectric Materials Doping for Enhancing the Built-In Electric Field of Perovskite Solar Cells Realizing Efficiency over 24.

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 FA0.92 MA0.08 PbI3 perovskite by doping an organic ferroelectric material, poly(vinylidene fluoride):dabcoHReO4 (PVDF:DH) with high polarizability, that can be driven even by the BEF of the device itself. The polarization of PVDF:DH produces an additional electric field, which is maintained permanently, in a direction consistent with that of the BEF of the pero-SC. The BEF superposition can more sufficiently drive the charge-carrier transport and extraction, thus suppressing the nonradiative recombination occurring in the pero-SCs. Moreover, the PVDF:DH dopant benefits the formation of a mesoporous PbI2 film, via a typical two-step processing method, thereby promoting perovskite growth with high crystallinity and a few defects. The resulting pero-SC shows a promising PCE of 24.23% for a 0.062 cm2 device (certified PCE of 23.45%), and a remarkable PCE of 22.69% for a 1 cm2 device, along with significantly improved moisture resistances and operational stabilities.

Multicolour Fluorescence Based on Excitation-Dependent Electron Transfer Processes in o-Carborane Dyads.

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.

A predictive model for vertebrate bone identification from collagen using proteomic mass spectrometry.

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.

Excitation Wavelength Dependent Fluorescence of an ESIPT Triazole Derivative for Amine Sensing and Anti-Counterfeiting Applications.

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.

Ratiometric Piezochromism of Electrospun Polymer Films: Intermolecular Interactions for Enhanced Sensitivity and Color Difference.

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.

Body fluid identification by mass spectrometry.

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.

Proteomic analysis of menstrual blood.

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.

Negative role of RIG-I serine 8 phosphorylation in the regulation of interferon-beta production.

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.

Employing a recombinant HLA-DR3 expression system to dissect major histocompatibility complex II-thyroglobulin peptide dynamism: a genetic, biochemical, and reverse immunological perspective.

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.

Mass spectrometric analysis reveals a functionally important PKA phosphorylation site in a Kir3 channel subunit.

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.

Aryl vinyl sulfonates and sulfones as active site-directed and mechanism-based probes for protein tyrosine phosphatases.

Protein tyrosine phosphatases (PTPs) play key roles in the regulation of normal and pathological processes ranging from cell proliferation, differentiation, metabolism, and survival to many human diseases including cancer and diabetes. Functional studies of PTP can be greatly facilitated by small molecule probes that covalently label the active site of a PTP through an activity-dependent chemical reaction. In this article, we characterize phenyl vinyl sulfonate (PVSN) and phenyl vinyl sulfone (PVS) as a new class of mechanism-based PTP probes. PVSN and PVS inactivate a broad range of PTPs in a time- and concentration-dependent fashion. The PVSN- and PVS-mediated PTP inactivation is active site-directed and irreversible, resulting from a Michael addition of the active-site Cys Sgamma onto the terminal carbon of the vinyl group. Structural and mechanistic analyses reveal the molecular basis for the preference of PVSN/PVS toward the PTPs, which lies in the ability of PVSN and PVS to engage the conserved structural and catalytic machinery of the PTP active site. In contrast to early alpha-bromobenzyl phosphonate-based probes, PVSN and PVS are resistant to solvolysis and are cell-permeable and thus hold promise for in vivo applications. Collectively, these properties bode well for the development of aryl vinyl sulfonate/sulfone-based PTP probes to interrogate PTP activity in complex proteomes.

Seminal plasma reduces the effectiveness of topical polyanionic microbicides.

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.

Global analysis of protein tyrosine phosphatase activity with ultra-sensitive fluorescent probes.

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.