Recent Stanford Publications in PubMedSubscribe to Recent Stanford Publications in PubMed
- Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis.Ye D, Shuhendler AJ, Pandit P, Brewer KD, Tee SS, Cui L, Tikhomirov G, Rutt B, Rao JChem Sci
- Neural correlates of intentional switching from ternary to binary meter in a musical hemiola pattern.Fujioka T, Fidali BC, Ross BFront Psychol
- A Three-Gene Assay for Monitoring Immune Quiescence in Kidney Transplantation.Roedder S, Li L, Alonso M, Hsieh SC, Vu MT, Dai H, Sigdel TK, Bostock I, Macedo C, Metes D, Zeevi A, Shapiro R, Salvatierra O, Scandling J, Alberu J, Engleman E, Sarwal MMJ Am Soc Nephrol
- Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa.Sebastiano V, Zhen HH, Derafshi BH, Bashkirova E, Melo SP, Wang P, Leung TL, Siprashvili Z, Tichy A, Li J, Ameen M, Hawkins J, Lee S, Li L, Schwertschkow A, Bauer G, Lisowski L, Kay MA, Kim SK, Lane AT, Wernig M, Oro AESci Transl Med
- Protective role of hemeoxygenase-1 in gastrointestinal diseases.Chang M, Xue J, Sharma V, Habtezion ACell Mol Life Sci
- Lipoprotein Phospholipase A2 Mass and Activity Are Not Associated with the Diagnosis of Acute Brain Ischemia.Tai W, Garcia M, Mlynash M, Kemp S, Albers GW, Olivot JMCerebrovasc Dis
- Inverse design and implementation of a wavelength demultiplexing grating coupler.Piggott AY, Lu J, Babinec TM, Lagoudakis KG, Petykiewicz J, Vučković JSci Rep
- Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients.Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FSNature
- Passive radiative cooling below ambient air temperature under direct sunlight.Raman AP, Anoma MA, Zhu L, Rephaeli E, Fan SNature
- Evolution in changing environments: Modifiers of mutation, recombination, and migration.Carja O, Liberman U, Feldman MWProc Natl Acad Sci U S A
Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis.
Chem Sci. 2014 Oct 1;4(10):3845-3852
Authors: Ye D, Shuhendler AJ, Pandit P, Brewer KD, Tee SS, Cui L, Tikhomirov G, Rutt B, Rao J
Non-invasive detection of caspase-3/7 activity in vivo has provided invaluable predictive information regarding tumor therapeutic efficacy and anti-tumor drug selection. Although a number of caspase-3/7 targeted fluorescence and positron emission tomography (PET) imaging probes have been developed, there is still a lack of gadolinium (Gd)-based magnetic resonance imaging (MRI) probes that enable high spatial resolution detection of caspase-3/7 activity in vivo. Here we employ a self-assembly approach and develop a caspase-3/7 activatable Gd-based MRI probe for monitoring tumor apoptosis in mice. Upon reduction and caspase-3/7 activation, the caspase-sensitive nano-aggregation MR probe (C-SNAM: 1) undergoes biocompatible intramolecular cyclization and subsequent self-assembly into Gd-nanoparticles (GdNPs). This results in enhanced r 1 relaxivity-19.0 (post-activation) vs. 10.2 mM(-1) s(-1) (pre-activation) at 1 T in solution-and prolonged accumulation in chemotherapy-induced apoptotic cells and tumors that express active caspase-3/7. We demonstrate that C-SNAM reports caspase-3/7 activity by generating a significantly brighter T 1-weighted MR signal compared to non-treated tumors following intravenous administration of C-SNAM, providing great potential for high-resolution imaging of tumor apoptosis in vivo.
PMID: 25429349 [PubMed - as supplied by publisher]
Neural correlates of intentional switching from ternary to binary meter in a musical hemiola pattern.
Front Psychol. 2014;5:1257
Authors: Fujioka T, Fidali BC, Ross B
Musical rhythms are often perceived and interpreted within a metrical framework that integrates timing information hierarchically based on interval ratios. Endogenous timing processes facilitate this metrical integration and allow us using the sensory context for predicting when an expected sensory event will happen ("predictive timing"). Previously, we showed that listening to metronomes and subjectively imagining the two different meters of march and waltz modulated the resulting auditory evoked responses in the temporal lobe and motor-related brain areas such as the motor cortex, basal ganglia, and cerebellum. Here we further explored the intentional transitions between the two metrical contexts, known as hemiola in the Western classical music dating back to the sixteenth century. We examined MEG from 12 musicians while they repeatedly listened to a sequence of 12 unaccented clicks with an interval of 390 ms, and tapped to them with the right hand according to a 3 + 3 + 2 + 2 + 2 hemiola accent pattern. While participants listened to the same metronome sequence and imagined the accents, their pattern of brain responses significantly changed just before the "pivot" point of metric transition from ternary to binary meter. Until 100 ms before the pivot point, brain activities were more similar to those in the simple ternary meter than those in the simple binary meter, but the pattern was reversed afterwards. A similar transition was also observed at the downbeat after the pivot. Brain areas related to the metric transition were identified from source reconstruction of the MEG using a beamformer and included auditory cortices, sensorimotor and premotor cortices, cerebellum, inferior/middle frontal gyrus, parahippocampal gyrus, inferior parietal lobule, cingulate cortex, and precuneus. The results strongly support that predictive timing processes related to auditory-motor, fronto-parietal, and medial limbic systems underlie metrical representation and its transitions.
PMID: 25429274 [PubMed - as supplied by publisher]
A Three-Gene Assay for Monitoring Immune Quiescence in Kidney Transplantation.
J Am Soc Nephrol. 2014 Nov 26;
Authors: Roedder S, Li L, Alonso M, Hsieh SC, Vu MT, Dai H, Sigdel TK, Bostock I, Macedo C, Metes D, Zeevi A, Shapiro R, Salvatierra O, Scandling J, Alberu J, Engleman E, Sarwal MM
Organ transplant recipients face life-long immunosuppression and consequently are at high risk of comorbidities. Occasionally, kidney transplant recipients develop a state of targeted immune quiescence (operational tolerance) against an HLA-mismatched graft, allowing them to withdraw all immunosuppression and retain stable graft function while resuming immune responses to third-party antigens. Methods to better understand and monitor this state of alloimmune quiescence by transcriptional profiling may reveal a gene signature that identifies patients for whom immunosuppression could be titrated to reduce patient and graft morbidities. Therefore, we investigated 571 unique peripheral blood samples from 348 HLA-mismatched renal transplant recipients and 101 nontransplant controls in a four-stage study including microarray, quantitative PCR, and flow cytometry analyses. We report a refined and highly validated (area under the curve, 0.95; 95% confidence interval, 0.92 to 0.97) peripheral blood three-gene assay (KLF6, BNC2, CYP1B1) to detect the state of operational tolerance by quantitative PCR. The frequency of predicted alloimmune quiescence in stable renal transplant patients receiving long-term immunosuppression (n=150) was 7.3% by the three-gene assay. Targeted cell sorting of peripheral blood from operationally tolerant patients showed a significant shift in the ratio of circulating monocyte-derived dendritic cells, with significantly different expression of the genes constituting the three-gene assay. Our results suggest that incorporation of patient screening by specific cellular and gene expression assays may support the safety of drug minimization trials and protocols.
PMID: 25429124 [PubMed - as supplied by publisher]
Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa.
Sci Transl Med. 2014 Nov 26;6(264):264ra163
Authors: Sebastiano V, Zhen HH, Derafshi BH, Bashkirova E, Melo SP, Wang P, Leung TL, Siprashvili Z, Tichy A, Li J, Ameen M, Hawkins J, Lee S, Li L, Schwertschkow A, Bauer G, Lisowski L, Kay MA, Kim SK, Lane AT, Wernig M, Oro AE
Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1-corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1-corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB.
PMID: 25429056 [PubMed - in process]
Protective role of hemeoxygenase-1 in gastrointestinal diseases.
Cell Mol Life Sci. 2014 Nov 27;
Authors: Chang M, Xue J, Sharma V, Habtezion A
Disorders and diseases of the gastrointestinal system encompass a wide array of pathogenic mechanisms as a result of genetic, infectious, neoplastic, and inflammatory conditions. Inflammatory diseases in general are rising in incidence and are emerging clinical problems in gastroenterology and hepatology. Hemeoxygenase-1 (HO-1) is a stress-inducible enzyme that has been shown to confer protection in various organ-system models. Its downstream effectors, carbon monoxide and biliverdin have also been shown to offer these beneficial effects. Many studies suggest that induction of HO-1 expression in gastrointestinal tissues and cells plays a critical role in cytoprotection and resolving inflammation as well as tissue injury. In this review, we examine the protective role of HO-1 and its downstream effectors in modulating inflammatory diseases of the upper (esophagus and stomach) and lower (small and large intestine) gastrointestinal tract, the liver, and the pancreas. Cytoprotective, anti-inflammatory, anti-proliferative, antioxidant, and anti-apoptotic activities of HO-1 make it a promising if not ideal therapeutic target for inflammatory diseases of the gastrointestinal system.
PMID: 25428780 [PubMed - as supplied by publisher]
Lipoprotein Phospholipase A2 Mass and Activity Are Not Associated with the Diagnosis of Acute Brain Ischemia.
Cerebrovasc Dis. 2014 Nov 21;38(5):324-327
Authors: Tai W, Garcia M, Mlynash M, Kemp S, Albers GW, Olivot JM
Background: Elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with both coronary artery and cerebrovascular diseases. The clinical diagnosis of neurovascular events, specifically transient ischemic attack can be challenging, although there is disagreement among vascular trained neurologists regarding this. Currently, there is no single accurate biomarker for the diagnosis of acute brain ischemia. Aim: We studied the relationship between Lp-PLA2 mass and activity levels and the diagnosis of acute brain ischemia in the acute phase among patients evaluated in the emergency department following transient focal neurological symptoms. Methods: Patients evaluated in our academic center for transient neurological symptoms of possible ischemic mechanism were enrolled with informed consent. Lp-PLA2 mass and activity levels were performed by DiaDexus, Inc. Results: 100 patients were enrolled: 58 were ischemic (30 stroke, 28 TIA), 10 were unknown, and 28 were non-ischemic. Blood samples were collected after a median delay of 23 h (IQR: 17, 36) after symptom onset. The median levels of Lp-PLA2 activity level for ischemic (stroke and TIA) versus non-ischemic events were 186.5 nmol/ml/min (IQR = 153, 216.3) and 169 nmol/ml/min (IQR = 137, 212.5), respectively. The median levels of Lp-PLA2 mass level for ischemic versus non-ischemic events were 202 ng/ml (IQR = 171.6, 226.1) and 192 ng/ml (167.8, 230). The differences in median Lp-PLA2 mass and activity levels were not statistically significant in the ischemic versus non-ischemic patients. Vessel imaging revealed a symptomatic stenosis in 14 patients (10 intracranial and 4 cervical). The median Lp-PLA2 mass and activity levels among patients with a symptomatic stenosis were not significantly higher than the levels measured in TIA/stroke patients without stenosis. Conclusion: The results of our study do not support the early measurement of Lp-PLA2 mass or activity levels for confirming an ischemic etiology in patients experiencing minor or transient focal neurological events. © 2014 S. Karger AG, Basel.
PMID: 25428761 [PubMed - as supplied by publisher]
Inverse design and implementation of a wavelength demultiplexing grating coupler.
Sci Rep. 2014;4:7210
Authors: Piggott AY, Lu J, Babinec TM, Lagoudakis KG, Petykiewicz J, Vučković J
Nanophotonics has emerged as a powerful tool for manipulating light on chips. Almost all of today's devices, however, have been designed using slow and ineffective brute-force search methods, leading in many cases to limited device performance. In this article, we provide a complete demonstration of our recently proposed inverse design technique, wherein the user specifies design constraints in the form of target fields rather than a dielectric constant profile, and in particular we use this method to demonstrate a new demultiplexing grating. The novel grating, which has not been developed using conventional techniques, accepts a vertical-incident Gaussian beam from a free-space and separates O-band (1300 nm) and C-band (1550 nm) light into separate waveguides. This inverse design concept is simple and extendable to a broad class of highly compact devices including frequency filters, mode converters, and spatial mode multiplexers.
PMID: 25428549 [PubMed - as supplied by publisher]
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients.
Nature. 2014 Nov 26;515(7528):563-7
Authors: Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS
The development of human cancer is a multistep process characterized by the accumulation of genetic and epigenetic alterations that drive or reflect tumour progression. These changes distinguish cancer cells from their normal counterparts, allowing tumours to be recognized as foreign by the immune system. However, tumours are rarely rejected spontaneously, reflecting their ability to maintain an immunosuppressive microenvironment. Programmed death-ligand 1 (PD-L1; also called B7-H1 or CD274), which is expressed on many cancer and immune cells, plays an important part in blocking the 'cancer immunity cycle' by binding programmed death-1 (PD-1) and B7.1 (CD80), both of which are negative regulators of T-lymphocyte activation. Binding of PD-L1 to its receptors suppresses T-cell migration, proliferation and secretion of cytotoxic mediators, and restricts tumour cell killing. The PD-L1-PD-1 axis protects the host from overactive T-effector cells not only in cancer but also during microbial infections. Blocking PD-L1 should therefore enhance anticancer immunity, but little is known about predictive factors of efficacy. This study was designed to evaluate the safety, activity and biomarkers of PD-L1 inhibition using the engineered humanized antibody MPDL3280A. Here we show that across multiple cancer types, responses (as evaluated by Response Evaluation Criteria in Solid Tumours, version 1.1) were observed in patients with tumours expressing high levels of PD-L1, especially when PD-L1 was expressed by tumour-infiltrating immune cells. Furthermore, responses were associated with T-helper type 1 (TH1) gene expression, CTLA4 expression and the absence of fractalkine (CX3CL1) in baseline tumour specimens. Together, these data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1, and is re-invigorated on antibody treatment.
PMID: 25428504 [PubMed - in process]
Passive radiative cooling below ambient air temperature under direct sunlight.
Nature. 2014 Nov 26;515(7528):540-4
Authors: Raman AP, Anoma MA, Zhu L, Rephaeli E, Fan S
Cooling is a significant end-use of energy globally and a major driver of peak electricity demand. Air conditioning, for example, accounts for nearly fifteen per cent of the primary energy used by buildings in the United States. A passive cooling strategy that cools without any electricity input could therefore have a significant impact on global energy consumption. To achieve cooling one needs to be able to reach and maintain a temperature below that of the ambient air. At night, passive cooling below ambient air temperature has been demonstrated using a technique known as radiative cooling, in which a device exposed to the sky is used to radiate heat to outer space through a transparency window in the atmosphere between 8 and 13 micrometres. Peak cooling demand, however, occurs during the daytime. Daytime radiative cooling to a temperature below ambient of a surface under direct sunlight has not been achieved because sky access during the day results in heating of the radiative cooler by the Sun. Here, we experimentally demonstrate radiative cooling to nearly 5 degrees Celsius below the ambient air temperature under direct sunlight. Using a thermal photonic approach, we introduce an integrated photonic solar reflector and thermal emitter consisting of seven layers of HfO2 and SiO2 that reflects 97 per cent of incident sunlight while emitting strongly and selectively in the atmospheric transparency window. When exposed to direct sunlight exceeding 850 watts per square metre on a rooftop, the photonic radiative cooler cools to 4.9 degrees Celsius below ambient air temperature, and has a cooling power of 40.1 watts per square metre at ambient air temperature. These results demonstrate that a tailored, photonic approach can fundamentally enable new technological possibilities for energy efficiency. Further, the cold darkness of the Universe can be used as a renewable thermodynamic resource, even during the hottest hours of the day.
PMID: 25428501 [PubMed - in process]
Evolution in changing environments: Modifiers of mutation, recombination, and migration.
Proc Natl Acad Sci U S A. 2014 Nov 26;
Authors: Carja O, Liberman U, Feldman MW
The production and maintenance of genetic and phenotypic diversity under temporally fluctuating selection and the signatures of environmental changes in the patterns of this variation have been important areas of focus in population genetics. On one hand, periods of constant selection pull the genetic makeup of populations toward local fitness optima. On the other, to cope with changes in the selection regime, populations may evolve mechanisms that create a diversity of genotypes. By tuning the rates at which variability is produced-such as the rates of recombination, mutation, or migration-populations may increase their long-term adaptability. Here we use theoretical models to gain insight into how the rates of these three evolutionary forces are shaped by fluctuating selection. We compare and contrast the evolution of recombination, mutation, and migration under similar patterns of environmental change and show that these three sources of phenotypic variation are surprisingly similar in their response to changing selection. We show that the shape, size, variance, and asymmetry of environmental fluctuation have different but predictable effects on evolutionary dynamics.
PMID: 25427794 [PubMed - as supplied by publisher]
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