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Clinical and animal studies have shown that coexpression of the receptor tyrosine kinases HER2 and epidermal growth factor (EGF) receptor (EGFR) indicates a highly metastatic phenotype of breast cancer. In a cellular model of this phenotype using differential gene expression analysis, we identified TOB1 to be up-regulated depending on EGF stimulation and transduction through phosphorylation of HER2 tyrosine 1248. mRNA expression analysis of breast cancers from a cohort of node-negative patients showed significantly shortened distant metastasis-free survival for patients with high TOB1 expression. In subsequent tissue microarray studies of 725 clinical samples, high HER2 and EGF protein levels were significantly correlated with TOB1 expression in breast cancer, whereas EGFR and EGF levels correlated with TOB1 phosphorylation. We did not observe a correlation between TOB1 expression and cyclin D1, which was previously suggested to mediate the antiproliferative effect of unphosphorylated TOB1. A positive correlation of TOB1 phosphorylation status with proliferation marker Ki67 suggests that elevated TOB1 phosphorylation might abrogate the antiproliferative effect of TOB1 in breast cancer. This suggests a new regulatory role for TOB1 in cancer progression with particular significance in HER2- and/or EGFR-positive breast cancers. [Cancer Res 2009;69(12):5049–56]

Supplementary Tables 1-8 from TOB1 Is Regulated by EGF-Dependent HER2 and EGFR Signaling, Is Highly Phosphorylated, and Indicates Poor Prognosis in Node-Negative Breast Cancer

Nonfullerene acceptors have recently emerged as promising candidates for organic photovoltaics (OPVs) owing to their superior optoelectronic properties. However, the varied lowest unoccupied molecular orbital (LUMO) levels of the acceptors pose difficulty in aligning their energy levels with existing electron transporting layers (ETLs). The authors propose here a facile design of the ETL with a tunable work function by simply varying the annealing temperature of titanium diisopropoxide bis(acetylacetonate) (TIAA) to change the molecular structure of the titanium complex. The energy level tuning is realized without changing the morphological features of the active layer, and as a result, it can enhance the charge extraction efficiency and thus ultimately the power conversion efficiency of the nonfullerene OPV. Our design will provide new important insights for achieving efficient nonfullerene OPVs.

Summary Organic photovoltaics (OPVs) have attracted considerable attention in recent years. Most reported strategies are from the perspective of the active layers to control the morphology of the donor/acceptor blend, with few methods focusing on modifying the transporting layers. Here, we develop a facile method to enhance both the thermal stability and efficiency of OPVs simultaneously from the perspective of the electron-transporting layer (ETL). Compared with traditional planar ETLs used in OPVs, our mesoporous ETL is designed to serve as a rigid scaffold to inhibit polymer diffusion upon heating. Furthermore, this structure creates more surface-area contact between the active layer and the ETL, potentially enhancing charge-extraction efficiency. As a result, the power-conversion efficiency (PCE) with this structure was enhanced by 11% relative to the planar structure. After being subjected to thermal stability test, the PCE of the mesoporous structure retained 69% of its original value.

Summary A tandem structure was invented to enhance photon utilization efficiency and reduce thermal loss. Considering the unique advantages of non-fullerene acceptors (NFAs), the combination of NFAs and the tandem concept shows great potential for organic photovoltaics (OPVs). Herein, a simple strategy to balance the voltage-current trade-off in tandem OPVs by employing mixed NFAs in rear sub-cells is reported. The VOC and JSC of rear sub-cells can be tuned by using the blend of donor/NFA/NFA. This strategy offers an easy approach to balance the VOC and JSC in tandem OPVs toward higher power conversion efficiency (PCE) without rational and careful synthesis of new materials. Tandem OPVs based on mixed NFAs in rear sub-cells exhibited the best PCE of 13.3% in the lab. Importantly, the tandem devices were certified by the National Renewable Energy Laboratory (NREL) under asymptotic scans, and a PCE of 11.52% was achieved and recognized on the most recent NREL chart.

Despite significant development recently, improving the power conversion efficiency of organic photovoltaics (OPVs) is still an ongoing challenge to overcome. One of the prerequisites to achieving this goal is to enable efficient charge separation and small voltage losses at the same time. In this work, a facile synthetic strategy is reported, where optoelectronic properties are delicately tuned by the introduction of electron-deficient-core-based fused structure into non-fullerene acceptors. Both devices exhibited a low voltage loss of 0.57 V and high short-circuit current density of 22.0 mA cm(-2), resulting in high power conversion efficiencies of over 13.4%. These unconventional electron-deficient-core-based non-fullerene acceptors with near-infrared absorption lead to low non-radiative recombination losses in the resulting organic photovoltaics, contributing to a certified high power conversion efficiency of 12.6%. Funding Agencies|Air Force Office of Scientific Research (AFOSR) [FA2386-15-1-4108, FA9550e15-1e0610, FA9550-15-1-0333]; UC-Solar Program [MRPI 328368]; National Key Research & Development Projects of China [2017YFA0206600]; National Natural Science Foundation of China [21875286]; Science Fund for Distinguished Young Scholars of Hunan Province [2017JJ1029]; Swedish Energy Agency Energimyndigheten [2016-010174]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]

Because the visible and the infrared (IR) regions take up ∼47% and ∼51% of the energy in the solar spectrum (AM 1.5G standard), respectively, utilizing the visible light for plant growth and the IR light for power generation is potentially extremely exciting. IR-absorbing organic semiconductors, with localized IR absorption and visible-light transmittance, would be promising materials for this purpose. Here, flexible transparent organic photovoltaics (TOPVs) based on IR-absorbing organic materials were proposed, which can be a simple, low-cost, and promising way to utilize the IR light for electricity generation, and the penetrated visible light will be utilized for photosynthesis in plants. A power-conversion efficiency of ∼10% with an average visible transmittance of 34% was achieved for TOPV devices. Meanwhile, the side-by-side comparison showed that plants grown under the TOPVs filtered light, and those under normal sunlight yielded very similar results. These outcomes demonstrated the results from TOPV devices beyond simple photovoltaic applications.

In light of the importance of and challenges inherent in realizing a wearable healthcare platform for simultaneously recognizing, preventing, and treating diseases while tracking vital signs, the development of simple and customized functional devices has been required. Here, we suggest a new approach to make a stretchable light waveguide which can be combined with integrated functional devices, such as organic photodetectors and nanowire-based heaters, for multifunctional healthcare monitoring. Controlling the reflection condition of the medium gave us a solid design rule for strong light emission in our stretchable waveguides. Based on this rule, the stretchable light waveguide (up to 50% strain) made of polydimethylsiloxane was successfully demonstrated with strong emissions. We also incorporated highly sensitive organic photodetectors and silver nanowire-based heaters with the stretchable waveguide for the detection of vital signs, including heart rate, deep breathing, coughs, and blood oxygen saturation. Through these multifunctional performances, we have successfully demonstrated that our stretchable light waveguide has a strong potential for multifunctional healthcare monitoring.

Summary In contrast to conventional colloidal quantum dots (CQDs), management of insulating ligands on perovskite CQDs is challenging because their ionic bonds are highly vulnerable to polar solvents. Consequently, there have been only a few examples of perovskite CQD solar cells incorporating relatively robust inorganic perovskite of which optoelectronic properties are not ideal for photovoltaic devices. Here, we report efficient and stable CQD solar cells based on formamidinium lead triiodide (FAPbI3) CQDs realized by rational surface regulation. Tailoring polarity of antisolvents for the post-synthetic process enabled effective removal of the insulating ligands on FAPbI3 CQDs while preserving perovskite cores. Owing to the enhanced inter-dot electrical coupling, a power-conversion efficiency of 8.38% was demonstrated. Furthermore, the FAPbI3 CQDs-based devices showed superior stability over those of bulk FAPbI3 devices. Thermodynamic and crystallographic analyses revealed that enhanced contribution of the surface energy and lattice contraction contribute to their superior stability.

Perovskite/CIGS tandem cells Tandem solar cells can boost efficiency by using more of the available solar spectrum. Han et al. fabricated a two-terminal tandem cell with an inorganicorganic hybrid perovskite top layer and a Cu(In,Ga)Se 2 (CIGS) bottom layer. Control of the roughness of the CIGS surface and the use of a heavily doped organic hole transport layer were crucial to achieve a 22.4% power conversion efficiency. The unencapsulated tandem cells maintained almost 90% of their efficiency after 500 hours of operation under ambient conditions. Science , this issue p. 904

Strain effects on vacancies, electronic states and stability have been disclosed for perovskite structured materials (ABX3) including metal oxides and organic-inorganic hybrids critical for energy storage and generation. Ion substitution has been pursued as an attractive solution to alter the crystallization or induced electronic of organic-inorganic hybrid halide lead perovskite. However, the disorganized structure of perovskite result from inappropriate substitution may cause unwanted phase transition and photo-stability. Herein, we introduce crystallization of restriction ABX3 composition with moderate zinc (Zn) substitution to obtain the ordered and stable CH3NH3(Zn:Pb)I3-xClx crystal, which is achieved via releasing lattice strain during an appropriate lattice constriction within BX6 octahedron. We obtained an unprecedented efficiency of 20.06% under simulated sunlight with facilitating binary metal perovskite of CH3NH3(1Zn:100Pb)I3-xClx. Our results are important to realize scale up and practical applications of efficient planar perovskite solar cells.

Summary Polymer photovoltaics have become a promising alternative energy due to lightweight properties, environmental friendliness, and solution processability. Transparent organic photovoltaics in particular have been recently receiving more attention in the photovoltaics field due to their unique potential in future applications beyond mere harvesting of solar energy. This perspective is further enhanced by the recent developments of high-performance polymer photovoltaics (including infrared absorbing materials and devices) that could achieve superior visible transparency and power conversion efficiency. To realize high-performance transparent organic photovoltaics, the main strategy is to shift the active-layer absorption spectrum to the infrared region by designing new low-bandgap donors and non-fullerene acceptors, and to reduce the invalid absorption by developing new transparent electrode materials. The potential applications are diverse, especially for spectrum-sensitive ones such as the greenhouse in agriculture. Finally, some key research areas of transparent organic photovoltaics that may deserve further attention are discussed.

The ionic nature of perovskite photovoltaic materials makes it easy to form various chemical interactions with different functional groups. Here, we demonstrate that interfacial chemical interactions are a critical factor in determining the optoelectronic properties of perovskite solar cells. By depositing different self-assembled monolayers (SAMs), we introduce different functional groups onto the SnO2 surface to form various chemical interactions with the perovskite layer. It is observed that the perovskite solar cell device performance shows an opposite trend to that of the energy level alignment theory, which shows that chemical interactions are the predominant factor governing the interfacial optoelectronic properties. Further analysis verifies that proper interfacial interactions can significantly reduce trap state density and facilitate the interfacial charge transfer. Through use of the 4-pyridinecarboxylic acid SAM, the resulting perovskite solar cell exhibits striking improvements to the reach t...

Despite significant development recently, improving the power conversion efficiency of organic photovoltaics (OPVs) is still an ongoing challenge to overcome. One of the prerequisites to achieving this goal is to enable efficient charge separation and small voltage losses at the same time. In this work, a facile synthetic strategy is reported, where optoelectronic properties are delicately tuned by the introduction of electron-deficient-core-based fused structure into non-fullerene acceptors. Both devices exhibited a low voltage loss of 0.57 V and high short-circuit current density of 22.0 mA cm−2, resulting in high power conversion efficiencies of over 13.4%. These unconventional electron-deficient-core-based non-fullerene acceptors with near-infrared absorption lead to low non-radiative recombination losses in the resulting organic photovoltaics, contributing to a certified high power conversion efficiency of 12.6%., Improving the power conversion efficiency is the main target of the organic solar cell research. Here Yuan et al. develop unconventional electron-deficient-core-based non-fullerene acceptors to achieve both low voltage loss and high current density, leading to a certified high efficiency of 12.6%.

The application of tandem structure that integrates multiple subcells into one device is a promising way to realize high efficiency organic solar cells. However, current-matching among different subcells remains as the main challenge for organic tandem photovoltaics. Here, we provide a facile approach to achieve a good current matching via engineering the chemical composition of non-fullerene ternary blend subcells. For the front subcell, a ternary blend of PDBT-T1:TPH-Se:ITIC is selected due to its good thermal stability. The amorphous nature of TPH-Se can sufficiently suppress the unfavorable phase separation of blends during the heat treatment, enabling a sintering in the fabrication of high quality interconnecting layer. A double-junction tandem device is fabricated with a rear subcell consisting of PBDB-T:ITIC. After the optimization of the chemical composition of the front subcell, the power conversion efficiency (PCE) of double-junction tandem device increased from 10.6% using PDBT-T1:TPH-Se binary front subcell to 11.5% using PDBT-T1:TPH-Se:ITIC (1:0.9:0.1) ternary front subcell due to better current matching. In order to further enhance the light absorption in the near-infrared region, a third junction PBDTTT-EFT:IEICO-4F is introduced. The champion cell of triple-junction non-fullerene tandem solar cell achieves a PCE of 13.0% with a high open circuit voltage of 2.52 V.

The electron transport layer (ETL) plays an important role in determining the device efficiency of organic solar cells (OSCs). A rational design of an ETL for OSCs targets high charge extraction and induction of an optimized active layer morphology. In this Letter, a high mobility In2O3 synthesized via a solution-processed combustion reaction is successfully used as a universal ETL in an organic photovoltaic device. With the modification of a thin layer of polyethylenimine ethoxylated (PEIE), a device based on crystalline In2O3 outperforms its counterpart, ZnO, in both PBDTTT-EFT-based fullerene and nonfullerene systems. As ZnO is replaced by In2O3, the average efficiency increases from 9.5% to 10.5% for PBDTTT-EFT–PC71BM fullerene-based organic solar cells and also increases from 10.8% to 11.5% for PBDTTT-EFT–IEICO-4F nonfullerene-based organic solar cells, respectively. Morphological studies have unraveled the fact that the crystalline In2O3 ETL with highly aligned nanocrystallites has induced the cryst...

Compositional engineering has been used to overcome difficulties in fabricating high-quality phase-pure formamidinium perovskite films together with its ambient instability. However, this comes alongside an undesirable increase in bandgap that sacrifices the device photocurrent. Here we report the fabrication of phase-pure formamidinium-lead tri-iodide perovskite films with excellent optoelectronic quality and stability. Incorporation of 1.67 mol% of 2D phenylethylammonium lead iodide into the precursor solution enables the formation of phase-pure formamidinium perovskite with an order of magnitude enhanced photoluminescence lifetime. The 2D perovskite spontaneously forms at grain boundaries to protect the formamidinium perovskite from moisture and suppress ion migration. A stabilized power conversion efficiency (PCE) of 20.64% (certified stabilized PCE of 19.77%) is achieved with a short-circuit current density exceeding 24 mA cm−2 and an open-circuit voltage of 1.130 V, corresponding to a loss-in-potential of 0.35 V, and significantly enhanced operational stability., Utilizing mixed-cation-halide can improve stability of the formamidinium perovskite films and devices but sacrifices the photocurrent due to an increase in bandgap. Here Lee et al. introduced small amounts of 2D perovskite to obtain high efficiency and stability based on phase-pure formamidinium based perovskite.

Incorporating narrow-bandgap near-infrared absorbers as the third component in a donor/acceptor binary blend is a new strategy to improve the power conversion efficiency (PCE) of organic photovoltaics (OPV). However, there are two main restrictions: potential charge recombination in the narrow-gap material and miscompatibility between each component. The optimized design is to employ a third component (structurally similar to the donor or acceptor) with a lowest unoccupied molecular orbital (LUMO) energy level similar to the acceptor and a highest occupied molecular orbital (HOMO) energy level similar to the donor. In this design, enhanced absorption of the active layer and enhanced charge transfer can be realized without breaking the optimized morphology of the active layer. Herein, in order to realize this design, two new narrow-bandgap nonfullerene acceptors with suitable energy levels and chemical structures are designed, synthesized, and employed as the third component in the donor/acceptor binary blend, which boosts the PCE of OPV to 11.6%.

The combination of hybrid perovskite and Cu(In,Ga)Se

Recently, a new type of active layer with a ternary system has been developed to further enhance the performance of binary system organic photovoltaics (OPV). In the ternary OPV, almost all active layers are formed by simple ternary blend in solution, which eventually leads to the disordered bulk heterojunction (BHJ) structure after a spin-coating process. There are two main restrictions in this disordered BHJ structure to obtain higher performance OPV. One is the isolated second donor or acceptor domains. The other is the invalid metal-semiconductor contact. Herein, the concept and design of donor/acceptor/acceptor ternary OPV with more controlled structure (C-ternary) is reported. The C-ternary OPV is fabricated by a sequential solution process, in which the second acceptor and donor/acceptor binary blend are sequentially spin-coated. After the device optimization, the power conversion efficiencies (PCEs) of all OPV with C-ternary are enhanced by 14-21% relative to those with the simple ternary blend; the best PCEs are 10.7 and 11.0% for fullerene-based and fullerene-free solar cells, respectively. Moreover, the averaged PCE value of 10.4% for fullerene-free solar cell measured in this study is in great agreement with the certified one of 10.32% obtained from Newport Corporation.

The morphology, photophysics, and device performance of solar cells based on the low bandgap polymer poly[[2,6'-4,8-di(5-ethylhexylthienyl)benzo[1,2-b;3,3-b]dithiophene]3-fluoro-2[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl (PBDTTT-EFT) (also known as PTB7-Th) blended with different fullerene acceptors: Phenyl-C-61-butyric acid methyl ester (PC61BM), phenyl-C-71-butyric acid methyl ester (PC71BM), or indene-C-60 bisadduct (ICBA) are correlated. Compared to PC71BM-based cells-which achieve a power conversion efficiency (PCE) of 9.4%-cells using ICBA achieve a higher open-circuit voltage (V-OC) of 1.0 V albeit with a lower PCE of 7.1%. To understand the origin of this lower PCE, the morphology and photophysics have been thoroughly characterized. Hard and soft X-ray scattering measurements reveal that the PBDTTT-EFT: ICBA blend has a lower crystallinity, lower domain purity, and smaller domain size compared to the PBDTTT-EFT: PC71BM blend. Incomplete photoluminescence quenching is also found in the ICBA blend with transient absorption measurements showing faster recombination dynamics at short timescales. Transient photovoltage measurements highlight further differences in recombination at longer timeframes due to the more intermixed morphology of the ICBA blend. Interestingly, a mild thermal treatment improves the performance of PBDTTT-EFT: ICBA cells which is exploited in the fabrication of a homo PBDTTT-EFT: ICBA tandem solar cell with PCE of 9.0% and V-OC of 1.93 V.

We investigated whether circulating monocytes from patients with systemic juvenile idiopathic arthritis (SJIA) are resistant to apoptosis and which apoptotic pathway(s) may mediate this resistance. A microarray analysis of peripheral blood mononuclear cells (PBMC) of SJIA samples and RT-PCR analysis of isolated monocytes showed that monocytes from active SJIA patients express transcripts that imply resistance to apoptosis. SJIA monocytes incubated in low serum show reduced annexin binding and diminished FasL up-regulation compared to controls. SJIA monocytes are less susceptible to anti-Fas-induced apoptosis and, upon activation of the mitochondrial pathway with staurosporine, show diminished Bid cleavage and Bcl-w down-regulation compared to controls. Exposure to SJIA plasma reduces responses to apoptotic triggers in normal monocytes. Thus, SJIA monocytes are resistant to apoptosis due to alterations in both the extrinsic and intrinsic apoptosis pathways, and circulating factors associated with active SJIA may confer this phenotype.

Clinical and animal studies have shown that coexpression of the receptor tyrosine kinases HER2 and epidermal growth factor (EGF) receptor (EGFR) indicates a highly metastatic phenotype of breast cancer. In a cellular model of this phenotype using differential gene expression analysis, we identified TOB1 to be up-regulated depending on EGF stimulation and transduction through phosphorylation of HER2 tyrosine 1248. mRNA expression analysis of breast cancers from a cohort of node-negative patients showed significantly shortened distant metastasis-free survival for patients with high TOB1 expression. In subsequent tissue microarray studies of 725 clinical samples, high HER2 and EGF protein levels were significantly correlated with TOB1 expression in breast cancer, whereas EGFR and EGF levels correlated with TOB1 phosphorylation. We did not observe a correlation between TOB1 expression and cyclin D1, which was previously suggested to mediate the antiproliferative effect of unphosphorylated TOB1. A positive correlation of TOB1 phosphorylation status with proliferation marker Ki67 suggests that elevated TOB1 phosphorylation might abrogate the antiproliferative effect of TOB1 in breast cancer. This suggests a new regulatory role for TOB1 in cancer progression with particular significance in HER2- and/or EGFR-positive breast cancers. [Cancer Res 2009;69(12):5049–56]

By considering the fault propagation behaviors in process systems with control loops, a fuzzy-logic based fault diagnosis strategy has been developed in the present work. The proposed fault diagnosis methods can be implemented in two stages. In the off-line preparation stage, the potential causes of a system hazard are identified by deterrnining the minimal cut sets of a fault tree. The occurrence order of observable fault symptoms is derived frorn the system digraph and then encoded into a set of IF-THEN rules. In the next on-line diagnosis stage, the occurrence indices of the top event and also the fault origins are computed in a fuzzy inference system based on real-time measurement data. Simulation studies have been carried out to demonstrate the feasibility of the proposed approach.

By incorporating digraph models, fault trees and fuzzy inference mechanisms in a unified framework, a novel approach for fault diagnosis is developed in this work. To relieve the on-line computation load, the fault origins considered in diagnosis are limited to the basic events in the cut sets of a given fault tree. The symptom occurrence order associated with each root cause is derived from system digraph with the qualitative simulation techniques. The implied candidate patterns are enumerated according to two proposed theorems and then encoded in the inference system with IF–THEN rules. The simulation results show that the proposed approach is not only feasible but also capable of identifying the most likely cause(s) of a hazardous event at the earliest possible time.

Organic tandem solar cells have two sub-cells vertically connected via a tunnel junction (or interconnecting layer, ICL), which the ICL plays a critical role of determining the performance of the tandem cell. In this manuscript, we report a new design of the ICL consisting of zirconium (IV) acetylacetonate (Zr-Acac) as the electron transport layer. The Zr-Acac has a suitable work function to pin the Fermi-level of the ICL and hence, can effectively behave as the charge recombination function for the tandem device. Comparing to the reference device consisting of ZnO ETL layer, the Zr-Acac ICL can effectively enhance the efficiency by 20%, from 8.4 to 10.1% power conversion efficiencies. More importantly, the Zr-Acac ETL layer functions effectively without thermal annealing, which not only simplifies the tandem solar cell processing, but also widens the front sub-cell material selection.

Multiple sclerosis (MS) is a common and severe neurological disorder associated with an autoimmune response directed against myelin components within the CNS. Lymphocyte activation, extravasation, and recruitment, as well as effector function, involves the turning on and off of a number of genes, thus triggering specific transcriptional pathways. The characterization of the transcriptome in MS lesions should provide a better understanding of the mechanisms that generate and sustain the pathogenic immune response in this disease. Here we performed transcriptional profiling of 56 relevant genes in brain specimens from eight MS patients and eight normal controls by kinetic RT-PCR. Results showed a high transcriptional activity for the gene coding for myelin basic protein (MBP); however, it was not differentially expressed in MS samples, suggesting that remyelination is an active process also in the noninflammatory brain. CD4 and HLA-DRα transcripts were dramatically increased in MS as compared with controls. This reveals a robust MHC class II up-regulation and suggests that Ag is being presented locally to activated T cells. Although analysis of cytokine and cytokine receptor genes expression showed predominantly increased levels of several Th1 molecules (TGF-β, RANTES, and macrophage-inflammatory protein (MIP)-1α) in MS samples, some Th2 genes (IL-3, IL-5, and IL-6/IL-6R) were found to be up-regulated as well. Similarly, both proinflammatory type (CCR1, CCR5) and immunomodulatory type (CCR4, CCR8) chemokine receptors were differentially expressed in the MS brain. Overall, our data suggest a complex regulation of the inflammatory response in human autoimmune demyelination.

Infection with the human immunodeficiency virus (HIV) leads to a decrease in CD4+ T cells and disease progression within a decade of seroconversion. However, a small group of infected people, despite being infected by HIV for 10 or more years, remain clinically asymptomatic and have stable CD4+ cell counts without taking antiretroviral medication. To determine why these individuals, known as long-term survivors (LTS), remain healthy, the hematological profiles, viral load and properties, HIV coreceptor genotype, and anti-HIV immune responses of these people were compared with those of individuals who have progressed to disease (Progressors) over the same time period. Unlike Progressors, LTS have a low circulating viral load and a low number of HIV-infected cells. These differences in the levels of the viral load were not associated with a dominant biologic viral phenotype, varying growth kinetics of the virus, mutation in the cellular CCR5 gene, or the presence of neutralizing antibodies. Importantly, the difference in viral load could be explained by the enhanced ability of CD8+ cells from LTS to suppress HIV replication. © 1998 by The American Society of Hematology.

By screening members of Finnish families displaying hereditary nonpolyposis colorectal cancer (HNPCC) for predisposing germline mutations in MSH2 and MLH1, we show that two mutations in MLH1 together account for 63% (19/30) of kindreds meeting international diagnostic criteria. Mutation 1, originally detected as a 165-base pair deletion in MLH1 cDNA comprising exon 16, was shown to consist of a 3.5-kilobase genomic deletion most likely resulting from Alu-mediated recombination. Mutation 2 destroys the splice acceptor site of exon 6. A simple diagnostic test based on polymerase chain reaction was designed for both mutations. Our results show that these two ancestral founding mutations account for a majority of Finnish HNPCC kindreds and represent the first report of Alu-mediated recombination causing a prevalent, dominantly inherited predisposition to cancer.

Systemic juvenile idiopathic arthritis (SJIA) is a chronic autoinflammatory condition. The association with macrophage activation syndrome, and the therapeutic efficacy of inhibiting monocyte-derived cytokines, has implicated these cells in SJIA pathogenesis. To characterize the activation state (classical/M1 vs. alternative/M2) of SJIA monocytes, we immunophenotyped monocytes using several approaches. Monocyte transcripts were analyzed by microarray and quantitative PCR. Surface proteins were measured at the single cell level using flow cytometry. Cytokine production was evaluated by intracellular staining and ELISA. CD14(++)CD16(-) and CD14(+)CD16(+) monocyte subsets are activated in SJIA. A mixed M1/M2 activation phenotype is apparent at the single cell level, especially during flare. Consistent with an M2 phenotype, SJIA monocytes produce IL-1β after LPS exposure, but do not secrete it. Despite the inflammatory nature of active SJIA, circulating monocytes demonstrate significant anti-inflammatory features. The persistence of some of these phenotypes during clinically inactive disease argues that this state reflects compensated inflammation.

Although several genes have been implicated in the development of the early-onset autosomal dominant form of Alzheimer's disease (AD), the genetics of late-onset AD (LOAD) is complex. Loci on several chromosomes have been linked to the disease, but so far only the apolipoprotein E gene has been consistently shown to be a risk factor. We have performed a large-scale single-nucleotide polymorphism (SNP)-based association study, across the region of linkage on chromosome 12, in multiple case-control series totaling 1,089 LOAD patients and 1,196 control subjects and report association with SNPs in the glyceraldehyde-3-phosphate dehydrogenase ( GAPD ) gene. Subsequent analysis of GAPD paralogs on other chromosomes demonstrated association with two other paralogs. A significant association between LOAD and a compound genotype of the three GAPD genes was observed in all three sample sets. Individually, these SNPs make differential contributions to disease risk in each of the casecontrol series, suggesting that variants in functionally similar genes may account for series-to-series heterogeneity of disease risk. Our observations raise the possibility that GAPD genes are AD risk factors, a hypothesis that is consistent with the role of GAPD in neuronal apoptosis.

Individuals repeatedly exposed to HIV, but who remain uninfected, form a population enriched for persons likely to have either natural or acquired resistance to the virus. We have studied four such exposed uninfected cohorts, representing 60 individuals, for evidence of protective immunity. This population included participants exposed to HIV through anal or vaginal receptive intercourse on multiple occasions over many years. We observed CD8+-cell noncytotoxic inhibition of HIV replication in acutely infected CD4+cells in the vast majority of individuals most recently exposed to the virus (within 1 year). The levels of this CD8+-cell response were sufficient to inhibit thein vitroinfection of the exposed subjects’ peripheral blood mononuclear cells. We found no evidence of a significant role for CCR5 Δ32 mutation in this population, nor did CD4+cell susceptibility to infection or HIV-specific cytotoxic T-lymphocytes correlate with resistance to infection in the individuals tested. Therefore, the observed strong noncytotoxic CD8+-cell anti-HIV responses may be an antiviral immune activity contributing to the apparent protection from infection in these exposed uninfected individuals.

We constructed internal controls (ICs) to provide assurance that clinical specimens are successfully amplified and detected. The IC nucleic acids contain primer binding regions identical to those of the target sequence and contain a unique probe binding region that differentiates the IC from amplified target nucleic acid. Because only 20 copies of the IC are introduced into each test sample, a positive IC signal indicates that amplification was sufficient to generate a positive signal from targets present at the limit of test sensitivity. The COBAS AMPLICOR Chlamydia trachomatis , Neisseria gonorrhoeae , Mycobacterium tuberculosis , and human hepatitis C virus tests exhibited inhibition rates ranging from 5 to 9%. Approximately 64% of these inhibitory specimens were not inhibitory when a second aliquot was tested. Because repeatedly inhibitory specimens were not reported as false negative and because additional infected specimens were detected during retesting, test sensitivities were 1 to 6% greater than they would have been if the IC had not been used.

Isoindigo based conducting polymers have attracted extensive interest for polymer solar cell application since isoindigo is a green material and renewable from plants. We have synthesized four soluble low band gap isoindigo based polymers (PCI) with cyclopentadithiophene (CPDT) as the donor unit and isoindigo (I) as the acceptor unit, decorated with two kinds of alkyl side chains, octyl (8) and 2-ethylhexyl (e), via the Stille cross-coupling reaction denoted as PC8I8, PC8Ie, PCeI8 and PCeIe. By changing the side chain of copolymers from linear (PC8I8) to branched (PCeIe), the λmax of absorption is blue shifted from 1.37 to 1.48 eV and the HOMO level is lowered from −5.24 to −5.45 eV. The changes are due to the twist coplanarity of the polymer backbone. The density functional theory calculation revealed that the dihedral angle of copolymers has been increased from 14° to 20°. The properties of PC8Ie and PCeI8 lie between those of PC8I8 and PCeIe. The type of the side chain plays a major role in determining the photovoltaic performance of copolymers. The branched side chain improves the solubility of the polymer and increases the effective phase separation between the copolymer and PCBM. This results in favorable nanomorphology of the active layer. Thus, PCeIe with branched side chains on both donor and acceptor units exhibits the best photovoltaic properties with a Voc of 0.80 eV, Jsc of 11.6 mA cm−2 and fill factor of 43.0% and power conversion efficiency of 4.0%. The power conversion efficiency of this type of polymer could be further improved by optimizing the fabrication conditions and interlayer modification. This study offers a useful guideline for the molecular design of high efficiency isoindigo-based polymer solar cells.

The development of low bandgap conducting polymers has made bulk heterojunction solar cells a viable low cost renewable energy source. The high boiling point of 1,8-diiodooctane (DIO) is usually used to control the morphology of the active layer consisting of a conducting polymer and PCBM, so that a high power conversion solar cell can be achieved. We report here an alternative approach using nonvolatile, crystalline and conducting P3HT as an effective morphology control agent. A model system of PCPDTBT/PC61BM was selected for this study. The change of optoelectronic properties with the introduction of P3HT was monitored by measuring the absorption spectra and charge carrier mobility, and the morphology change with the introduction of P3HT in the active layer was monitored by AFM, TEM, and GIXRD. The results indicate that favorable bi-continuous phase separation and appropriate domain size of each phase can be achieved to facilitate fast charge transport, and thus improve the power conversion efficiency of the solar cell. By adding 1 wt% P3HT into the blend of PCPDTBT/PC61BM, the power conversion efficiency can be improved by 20%. Moreover, with the incorporation of 1 wt% P3HT to the blend of PCPDTBT/PC61BM with DIO, the power conversion efficiency can be further increased by 17%. The strategy of this study can be expanded to other low bandgap conducting polymers for high efficiency bulk heterojunction solar cells.

Solvent additive processing has become the most effective method to tune the nanostructure of donor–acceptor (D–A) type copolymer/fullerene bulk heterojunctions (BHJs) solar cells for improving power conversion efficiencies. However, to date qualitative microscopic observations reveal discrepant results on the effects of solvent additives. Here, we present quantitative evolution of bi-hierarchical nanostructure of D–A copolymers and fullerenes by employing grazing-incidence small/wide angle X-ray scattering (GISAXS/GIWAXS) techniques and [2,6-(4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b′]-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)]/[6,6]-phenyl-C71-butyric acid methyl ester (PCPDTBT/PCBM) BHJ as model materials. An accurate GISAXS model analysis is established herein for revealing the distinctive bi-hierarchical nanostructures from molecular level to a scale of hundreds of nanometers. The mechanisms of hierarchical formation and mutual influence between PCPDTBT and PCBM domains are proposed to correlate with photovoltaic properties. These results provide a comprehensive interpretation in respect to previous studies on the nanostructures of D–A copolymer/fullerene BHJs. It is helpful for optimum structural design and associated synthesis improvement for achieving high efficiency BHJ solar cells.

Systemic juvenile idiopathic arthritis (SJIA) is a chronic autoinflammatory condition of childhood, characterized by remitting fever, transient rash, and relapsing arthritis. The association of macrophage activation syndrome with SJIA and clinical evidence implicating monocyte-derived cytokines IL-1 and IL-6 suggest a key role for monocyte in SJIA pathogenesis. We have previously found monocyte expansion during disease activity (flare), and a normal distribution of the monocyte subsets CD14hiCD16- and CD14loCD16+. We also observed elevated expression of monocyte surface markers CD14 and CD16 in the respective CD14hiCD16- and CD14loCD16+ monocyte subpopulations during disease flare and inactivity (quiescence), suggesting phenotypic alteration of monocytes in SJIA, independent of clinical status. We further analyzed phenotypic and functional alterations of SJIA monocytes in relation to disease activity and in comparison to age- and ethnicity-matched controls, specifically regarding development towards a M1- or M2- polarized phenotype. Gene expression profile, flow-cytometry based analysis of surface markers, baseline and LPS-induced production of cytokines and phosphorylation patterns in response to cytokine stimulation indicate that SJIA monocytes have a mixed M1/M2 phenotype during disease flare. Disease quiescence is associated not with normalization, but with an M2 phenotype, suggesting the existence of a state of compensated inflammation that is broke during disease flare.

Publisher Summary The retroviruses associated with autoimmune deficiency syndrome (AIDS)—namely, human immunodeficiency virus types 1 and 2 (HIV-1, -2), display considerable genome sequence variability not only between isolates from different individuals but also between isolates from the same individual over time. This diversity is largely because of the extensive misincorporation of nucleotides by the viral reverse transcriptase, which lacks the proofreading 3 ' →5 ' -exonuclease activity. The conventional methods for molecular characterization of viral isolates involve cultivation of the agent, extraction of nucleic acid, and analysis by restriction enzyme mapping. Higher analytical resolution generally requires more time-consuming procedures, such as molecular cloning and sequencing of entire genomes. The PCR provides a rapid means for analyzing genomic diversity. There are two major advantages in using the PCR to study viral variants— (1) it obviates the need to propagate the virus in culture (a procedure that is expensive, time-consuming, and biohazardous) and (2) PCR allows detecting naturally occurring isolates and circumvents the viral selection, which often occurs during cultivation. The protocols for amplification, cloning, and sequencing of naturally occurring variants are presented in the chapter.

A preliminary design was made of a national user facility for evaluating magnetic-levitation (maglev) technologies in sizes intermediate between laboratory experiments and full-scale systems. A technical advisory committee was established and a conference was held to obtain advice on the potential requirements of operational systems and how the facility might best be configured to test these requirements. The effort included studies of multiple concepts for levitating, guiding, and propelling maglev vehicles, as well as the controls, communications, and data-acquisition and -reduction equipment that would be required in operating the facility. Preliminary designs for versatile, dual 2-MVA power supplies capable of powering attractive or repulsive systems were developed. Facility site requirements were identified. Test vehicles would be about 7.4 m (25 ft) long, would weigh form 3 to 7 metric tons, and would operate at speeds up to 67 m/s (150 mph) on a 3.3-km (2.05-mi) elevated guideway. The facility would utilize modular vehicles and guideways, permitting the substitution of levitation, propulsion, and guideway components of different designs and materials for evaluation. The vehicle would provide a test cell in which individual suspension or propulsion components or subsystems could be tested under realistic conditions. The system would allow economical evaluation ofmore » integrated systems under varying weather conditions and in realistic geometries.« less