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Sample records for molecule programmed death-1

  1. Costimulatory molecule programmed death-1 in the cytotoxic response during chronic hepatitis C.

    PubMed

    Larrubia, Juan-Ramón; Benito-Martínez, Selma; Miquel, Joaquín; Calvino, Miryam; Sanz-de-Villalobos, Eduardo; Parra-Cid, Trinidad

    2009-11-01

    Hepatitis C virus (HCV)-specific CD8(+) T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the virus. HCV has developed several mechanisms to escape immune control. One of these strategies is the up-regulation of negative co-stimulatory molecules such us programmed death-1 (PD-1). This molecule is up-regulated on intrahepatic and peripheral HCV-specific cytotoxic T cells during acute and chronic phases of the disease, whereas PD-1 expression is low in resolved infection. PD-1 expressing HCV-specific CD8(+) T cells are exhausted with impairment of several effector mechanisms, such as: type-1 cytokine production, expansion ability after antigen encounter and cytotoxic ability. However, PD-1 associated exhaustion can be restored by blocking the interaction between PD-1 and its ligand (PD-L1). After this blockade, HCV-specific CD8(+) T cells reacquire their functionality. Nevertheless, functional restoration depends on PD-1 expression level. High PD-1-expressing intrahepatic HCV-specific CD8(+) T cells do not restore their effector abilities after PD-1/PD-L1 blockade. The mechanisms by which HCV is able to induce PD-1 up-regulation to escape immune control are unknown. Persistent TCR stimulation by a high level of HCV antigens could favour early PD-1 induction, but the interaction between HCV core protein and gC1q receptor could also participate in this process. The PD-1/PD-L1 pathway modulation could be a therapeutic strategy, in conjunction with the regulation of others co-stimulatory pathways, in order to restore immune response against HCV to succeed in clearing the infection. PMID:19891011

  2. Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma.

    PubMed

    Schlößer, Hans A; Drebber, Uta; Kloth, Michael; Thelen, Martin; Rothschild, Sacha I; Haase, Simon; Garcia-Marquez, Maria; Wennhold, Kerstin; Berlth, Felix; Urbanski, Alexander; Alakus, Hakan; Schauss, Astrid; Shimabukuro-Vornhagen, Alexander; Theurich, Sebastian; Warnecke-Ebertz, Ute; Stippel, Dirk L; Zippelius, Alfred; Büttner, Reinhard; Hallek, Michael; Hölscher, Arnulf H; Zander, Thomas; Mönig, Stefan P; von Bergwelt-Baildon, Michael

    2016-05-01

    Remarkable efficacy of immune checkpoint inhibition has been reported for several types of solid tumors and early studies in gastric adenocarcinoma are promising. A detailed knowledge about the natural biology of immune checkpoints in gastric adenocarcinoma is essential for clinical and translational evaluation of these drugs. This study is a comprehensive analysis of cytotoxic T lymphocyte associated molecule 4 (CTLA-4) and programmed death 1 ligand 1 (PD-L1) expression in gastric adenocarcinoma. PD-L1 and CTLA-4 were stained on tumor sections of 127 Caucasian patients with gastric adenocarcinoma by immunohistochemistry (IHC) and somatic mutation profiling was performed using targeted next-generation sequencing. Expression of PD-L1 and CTLA-4 on lymphocytes in tumor sections, tumor-draining lymph nodes (TDLN) and peripheral blood were studied by flow-cytometry and immune-fluorescence microscopy in an additional cohort. PD-L1 and CTLA-4 were expressed in 44.9% (57/127) and 86.6% (110/127) of the analyzed gastric adenocarcinoma samples, respectively. Positive tumor cell staining for PD-L1 or CTLA-4 was associated with inferior overall survival. Somatic mutational analysis did not reveal a correlation to expression of PD-L1 or CTLA-4 on tumor cells. Expression of PD-1 (52.2%), PD-L1 (42.2%) and CTLA-4 (1.6%) on tumor infiltrating T cells was significantly elevated compared to peripheral blood. Of note, PD-1 and PD-L1 were expressed far higher by tumor-infiltrating lymphocytes than CTLA-4. In conclusion, specific immune checkpoint-inhibitors should be evaluated in this disease and the combination with molecular targeted therapies might be of benefit. An extensive immune monitoring should accompany these studies to better understand their mode of action in the tumor microenvironment. PMID:27467911

  3. Predictive Efficacy Biomarkers of Programmed Cell Death 1/Programmed Cell Death 1 Ligand Blockade Therapy.

    PubMed

    Fang, Xiao-Na; Fu, Li-Wu

    2016-01-01

    Inhibitors of immune check-point molecule, programmed cell death 1 (PD-1) and its ligand, programmed cell death ligand 1 (PD-L1) have attracted much attention in cancer immunotherapy recently due to their durable antitumor effects in various malignances, especially the advanced ones. Unfortunately, only a fraction of patients with advanced tumors could benefit from anti-PD-1/PD-L1 therapy, while others still worsened. The key to this point is that there are no efficient biomarkers for screening anti-PD-1/PD-L1-sensitive patients. In this review, we aim at summarizing the latest advances of anti-PD-1/PDL1 immunotherapy and the potential predictive efficacy biomarkers to provide evidences for identifying anti-PD-1/PDL1- sensitive patients. The present article also includes the patent review coverage on this topic. PMID:26916881

  4. Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

    PubMed

    Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

    2015-01-01

    Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit. PMID:26250412

  5. The Efficacy and Safety of Programmed Cell Death 1 and Programmed Cell Death 1 Ligand Inhibitors for Advanced Melanoma

    PubMed Central

    Guan, Xiuwen; Wang, Haijuan; Ma, Fei; Qian, Haili; Yi, Zongbi; Xu, Binghe

    2016-01-01

    Abstract The purpose of this study was to investigate the efficacy and safety of programmed cell death 1 (PD-1) and programmed cell death 1 ligand (PD-L1) inhibitors using a meta-analysis of present trials for advanced melanoma. A fully recursive literature search of the primary electronic databases for available trials was performed. The objective response rate (ORR) and the median progression-free survival (PFS) of clinical responses were considered the main endpoints to evaluate the efficacy, whereas Grade 3–4 adverse effects (AEs) were analyzed to evaluate safety. The ORR of PD-1 and PD-L1 inhibitors was 30% (95% CI: 25–35%). No significant difference in the ORR was observed after the comparisons of low-dose, median-dose, and high-dose cohorts. In addition, the rate of Grade 3–4 AEs was 9% (95% CI: 6–12%). According to the 3 randomized controlled trials that compared PD-1 inhibitors with chemotherapy, the difference between these 2 groups was found to be statistically significant with respect to the ORR, PFS and the incidence of Grade 3–4 AEs; that is, the relative risk (RR) of the ORR was 3.42 (95% CI: 2.49–4.69, P < 0.001), the hazard ratio (HR) of the PFS was 0.50 (95% CI: 0.44–0.58, P < 0.001), and the RR of Grade 3–4 AEs was 0.45 (95% CI: 0.31–0.65, P < 0.001). According to a meta-analysis of limited concurrent studies, PD-1 and PD-L1 inhibitors appear to be associated with improved response rates, superior response durability and tolerable toxicity in patients with advanced melanoma. PMID:26986169

  6. Analysis of Programmed Death-1 in Patients with Psoriatic Arthritis.

    PubMed

    Peled, Michael; Strazza, Marianne; Azoulay-Alfaguter, Inbar; Silverman, Gregg J; Scher, Jose U; Mor, Adam

    2015-08-01

    Programmed death-1 (PD-1) is an inhibitory co-receptor that is highly expressed in T lymphocytes that has been shown to downregulate inflammatory responses in several inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis. Yet, the role of PD-1 in psoriatic arthritis (PsA) has not been studied. In order to fill this gap, we measured the expression levels of PD-1 in peripheral T cells from patients with active disease. Twenty patients and fifteen age-matched healthy control subjects were recruited. The percentage of CD3(+)PD-1(+) T cells was measured by flow cytometry. Despite normal concentration of peripheral T cells, the expression levels of PD-1 were significantly higher in patients compared to healthy controls. Interestingly, among the patients, the expression levels inversely correlated with disease activity measured by disease activity scores (DAS28). PD-1 expression levels strongly correlated with the number of tender and swollen joints, but not with C-reactive protein (CRP) levels or psoriasis area and severity index (PASI). Functionally, in vitro ligation of PD-1 receptor in PsA T cells inhibited interleukin-2 (IL-2) secretion, Akt phosphorylation, and Rap1 activation. These findings suggest that PD-1 might serve as a biomarker for disease activity in PsA and highlight the need for additional studies in order to establish the role of PD-1 in PsA pathogenesis. PMID:25663558

  7. New-onset toxicity with programmed death-1 inhibitor rechallenge.

    PubMed

    Ludlow, Steven P; Andrews, Stephanie; Pasikhova, Yanina; Hill, Eboné

    2016-06-01

    Immunotherapy has become a mainstay in the treatment of metastatic melanoma. Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitors and programmed death-1 (PD-1) inhibitors, which have been added more recently, represent two of the main classes of immunomodulating agents. PD-1 inhibitors are well tolerated and are known to have a decreased rate of occurrence of adverse effects compared with CTLA-4 inhibitors. However, the risk remains for serious immune-mediated adverse reactions. Given their long half and extended efficacy, treatment with a CTLA-4 inhibitor before use of a PD-1 inhibitor may increase the risk of adverse effects. In addition, caution should be exercised when rechallenging grade 3 or 4 adverse effects with the same agent or a different agent of the same class. The re-emergence of a previous toxicity may occur or, as found in this case, a new severe effect may arise. This article will present a case of fatal immune-related hepatoxicity in a patient treated with a CTLA-4 inhibitor, followed by treatment with a PD-1 inhibitor. The mechanisms of action and safety profiles for both classes of drugs will also be reviewed. PMID:26983078

  8. Development of amino- and dimethylcarbamate-substituted resorcinol as programmed cell death-1 (PD-1) inhibitor.

    PubMed

    Liu, An; Dong, Lei; Wei, Xiao-Li; Yang, Xiao-Hong; Xiao, Jun-Hai; Liu, Zai-Qun

    2016-06-10

    Blockading the interaction of programmed death-1 (PD-1) protein with its ligands (PD-Ls, such as PD-L1) was proved to be a pathway for suppressing the development of tumors and other degradations of biological species. Thus, finding PD-1 inhibitors situated at the convergence point of drug discovery. In addition to some monoclonal antibodies applied to treat cancers clinically, the screening of organic molecules for hindering the interaction of PD-1 with PD-L1 became an efficient strategy in the development of PD-1 inhibitors. We herein applied resorcinol and 3-hydroxythiophenol as the core to link with N,N-dimethylcarbamate and other alkyl-substituted amines to afford 13 amine-appended phenyl dimethylcarbamates (AAPDs). The test for blockading the combination of PD-1 with PD-L1 revealed that abilities of 13 AAPDs were higher than that of sulfamethizole, a successful PD-1 inhibitor. In particular, large hydrophobic substituents at amine moiety or a nitro at resorcinol skeleton enhanced the inhibitory effect of AAPD even higher than that of sulfamethoxypyridazine, another successful PD-1 inhibitor. The present results may provide valuable information for further investigation on synthetic PD-1 inhibitors. PMID:27063329

  9. Regulation of Neuroinflammation through Programed Death-1/Programed Death Ligand Signaling in Neurological Disorders

    PubMed Central

    Zhao, Shangfeng; Li, Fengwu; Leak, Rehana K.; Chen, Jun; Hu, Xiaoming

    2014-01-01

    Immune responses in the central nervous system (CNS), which involve both resident glial cells and infiltrating peripheral immune cells, play critical roles in the progress of brain injuries and neurodegeneration. To avoid inflammatory damage to the compromised brain, the immune cell activities in the CNS are controlled by a plethora of chemical mediators and signal transduction cascades, such as inhibitory signaling through programed death-1 (PD-1) and programed death ligand (PD-L) interactions. An increasing number of recent studies have highlighted the importance of PD-1/PD-L pathway in immune regulation in CNS disorders such as ischemic stroke, multiple sclerosis, and Alzheimer’s disease. Here, we review the current knowledge of the impact of PD-1/PD-L signaling on brain injury and neurodegeneration. An improved understanding of the function of PD-1/PD-L in the cross-talk between peripheral immune cells, CNS glial cells, and non-immune CNS cells is expected to shed further light on immunomodulation and help develop effective and safe immunotherapies for CNS disorders. PMID:25232304

  10. Anti program death-1/anti program death-ligand 1 in digestive cancers

    PubMed Central

    de Guillebon, Eléonore; Roussille, Pauline; Frouin, Eric; Tougeron, David

    2015-01-01

    Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1 (PD-1) and program death-ligand 1 (PD-L1) will lead the activated T cell to a state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1 and anti-PD-L1 monoclonal antibodies (mAbs), called immune checkpoint inhibitors (ICIs), have consequently been designed to restore T cell activity. Accumulating data are in favor of an association between PD-L1 expression in tumors and response to treatment. A PD-L1 expression is present in 30% to 50% of digestive cancers. Multiple anti-PD-1 (nivolumab, pembrolizumab) and anti-PD-L1 mAbs (MPDL3280A, Medi4736) are under evaluation in digestive cancers. Preliminary results in metastatic gastric cancer with pembrolizumab are highly promising and phase II will start soon. In metastatic colorectal cancer (CRC), a phase III trial of MPDL3280A as maintenance therapy will shortly be initiated. Trials are also ongoing in metastatic CRC with high immune T cell infiltration (i.e., microsatellite instability). Major challenges are ahead in order to determine how, when and for which patients we should use these ICIs. New radiologic criteria to evaluate tumor response to ICIs are awaiting prospective validation. The optimal therapeutic sequence and association with cytotoxic chemotherapy needs to be established. Finally, biomarker identification will be crucial to selection of patients likely to benefit from ICIs. PMID:26306141

  11. Regulation of postsurgical fibrosis by the programmed death-1 inhibitory pathway.

    PubMed

    Holsti, Matthew A; Chitnis, Tanuja; Panzo, Ronald J; Bronson, Roderick T; Yagita, Hideo; Sayegh, Mohamed H; Tzianabos, Arthur O

    2004-05-01

    Surgical adhesions are a common and often severe complication of abdominal or pelvic injury that cause pelvic pain, bowel obstruction, and infertility in women. Current treatments are of limited effectiveness because little is known about the cellular and subcellular processes underlying adhesiogenesis. Recently, we showed that Th1 alpha beta CD4(+) T cells mediate the pathogenesis of adhesion formation in a rodent model of this disease process. In this study, we demonstrate that in mice these T cells home directly to the site of surgically induced adhesions and control local chemokine production in a manner dependent on the CD28 T cell costimulatory pathway. Conversely, the inhibitory programmed death-1 pathway plays a central role in limiting adhesiogenesis, as programmed death-1 blockade was associated with increased T cell infiltration, chemokine production, and a concomitant exacerbation of disease. Our results reveal for the first time that the development of postsurgical fibrosis is under the tight control of positive and negative T cell costimulation, and suggest that targeting these pathways may provide promising therapies for the prevention of adhesion formation. PMID:15100324

  12. Association of Acute Interstitial Nephritis With Programmed Cell Death 1 Inhibitor Therapy in Lung Cancer Patients.

    PubMed

    Shirali, Anushree C; Perazella, Mark A; Gettinger, Scott

    2016-08-01

    Immune checkpoint inhibitors that target the programmed death 1 (PD-1) signaling pathway have recently been approved for use in advanced pretreated non-small cell lung cancer and melanoma. Clinical trial data suggest that these drugs may have adverse effects on the kidney, but these effects have not been well described. We present 6 cases of acute kidney injury in patients with lung cancer who received anti-PD-1 antibodies, with each case displaying evidence of acute interstitial nephritis (AIN) on kidney biopsy. All patients were also treated with other drugs (proton pump inhibitors and nonsteroidal anti-inflammatory drugs) linked to AIN, but in most cases, use of these drugs long preceded PD-1 inhibitor therapy. The association of AIN with these drugs in our patients raises the possibility that PD-1 inhibitor therapy may release suppression of T-cell immunity that normally permits renal tolerance of drugs known to be associated with AIN. PMID:27113507

  13. Programmed death-1/programmed death-L1 signaling pathway and its blockade in hepatitis C virus immunotherapy

    PubMed Central

    Salem, Mohamed L; El-Badawy, Ahmed

    2015-01-01

    Chronic hepatitis C virus (HCV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses to HCV are key features of chronic HCV infection. Therefore, intervention strategies usually involve enhancing the immune responses against HCV. Cytotoxic CD8+ T lymphocytes (CTLs) play a critical role in the control of HCV infection. However, their cytolytic function can be impaired by the expression of co-inhibitory molecules. Programmed death-1 (PD-1) receptor and its ligand PD-L1 function in a T cell co-inhibitory pathway, which either blocks the function of CTLs or the differentiation of CD8+ T cells. During chronic HCV infection, the immune inhibitory receptor PD-1 is upregulated on dysfunctional HCV-specific CD8+ T cells. As such, blockade of the PD-1/PD-L1 pathway in these CD8+ T cells might restore their functional capabilities. Indeed, clinical trials using therapies to block this pathway have shown promise in the fostering of anti-HCV immunity. Understanding how chronic HCV infection induces upregulation of PD-1 on HCV specific T cells and how the PD-1/PD-L1 interaction develops HCV specific T cell dysfunction will accelerate the development of an efficacious prophylactic and therapeutic vaccination against chronic HCV infections, which will significantly improve HCV treatments and patient survival. In this review, we discuss the relationship between PD-1 expression and clinical responses and the potential use of PD-1 blockade for anti-HCV therapy. PMID:26483866

  14. Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice.

    PubMed

    Frebel, Helge; Nindl, Veronika; Schuepbach, Reto A; Braunschweiler, Thomas; Richter, Kirsten; Vogel, Johannes; Wagner, Carsten A; Loffing-Cueni, Dominique; Kurrer, Michael; Ludewig, Burkhard; Oxenius, Annette

    2012-12-17

    The inhibitory programmed death 1 (PD-1)-programmed death ligand 1 (PD-L1) pathway contributes to the functional down-regulation of T cell responses during persistent systemic and local virus infections. The blockade of PD-1-PD-L1-mediated inhibition is considered as a therapeutic approach to reinvigorate antiviral T cell responses. Yet previous studies reported that PD-L1-deficient mice develop fatal pathology during early systemic lymphocytic choriomeningitis virus (LCMV) infection, suggesting a host protective role of T cell down-regulation. As the exact mechanisms of pathology development remained unclear, we set out to delineate in detail the underlying pathogenesis. Mice deficient in PD-1-PD-L1 signaling or lacking PD-1 signaling in CD8 T cells succumbed to fatal CD8 T cell-mediated immunopathology early after systemic LCMV infection. In the absence of regulation via PD-1, CD8 T cells killed infected vascular endothelial cells via perforin-mediated cytolysis, thereby severely compromising vascular integrity. This resulted in systemic vascular leakage and a consequential collapse of the circulatory system. Our results indicate that the PD-1-PD-L1 pathway protects the vascular system from severe CD8 T cell-mediated damage during early systemic LCMV infection, highlighting a pivotal physiological role of T cell down-regulation and suggesting the potential development of immunopathological side effects when interfering with the PD-1-PD-L1 pathway during systemic virus infections. PMID:23230000

  15. Nivolumab, an Anti-Programmed Cell Death-1 Antibody, Induces Fulminant Type 1 Diabetes.

    PubMed

    Miyoshi, Yuka; Ogawa, Osamu; Oyama, Yu

    2016-01-01

    Programmed cell death-1 (PD-1), an immunoreceptor, is located on T cells and pro-B cells and interacts with its ligands to inhibit T cell activation and proliferation, thereby promoting immunological self-tolerance. Nivolumab, an anti-PD1 antibody, blocks PD-1 and can restore anticancer immune responses by abrogating PD-1 pathway-mediated T-cell inhibition. Autoimmune adverse events are expected with PD-1 therapy. Fulminant type 1 diabetes is the subtype of type 1 diabetes. The clinical feature is the extremely rapid progression of hyperglycemia and ketoacidosis. Here we describe a 66-year-old woman with advanced melanoma who was treated with nivolumab. After 4 months and six doses of the medicine, the patient was admitted to the hospital with complaints of nausea and vomiting. The laboratory data showed ketonuria, hyperglycemia (531 mg/dl), high anion gap metabolic acidosis, HbA1c (7.3%), and absence of insulin-secreting capacity. These data are compatible with the criteria of fulminant type 1 diabetes. The patient was diagnosed with diabetic ketoacidosis because of fulminant type 1 diabetes. The findings of this case indicated that nivolumab can cause fulminant type 1 diabetes. Diabetic ketoacidosis due to fulminant type 1 diabetes is potentially fatal condition. Thus, diabetic ketoacidosis due to fulminant type 1 diabetes should be considered in the differential diagnosis when patients treated with nivolumab complain of gastrointestinal symptoms. PMID:27297738

  16. Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1).

    PubMed

    Fuller, Michael J; Callendret, Benoit; Zhu, Baogong; Freeman, Gordon J; Hasselschwert, Dana L; Satterfield, William; Sharpe, Arlene H; Dustin, Lynn B; Rice, Charles M; Grakoui, Arash; Ahmed, Rafi; Walker, Christopher M

    2013-09-10

    Hepatitis C virus (HCV) persistence is facilitated by exhaustion of CD8+ T cells that express the inhibitory receptor programmed cell death 1 (PD-1). Blockade of PD-1 signaling improves in vitro proliferation of HCV-specific T lymphocytes, but whether antiviral function can be restored in infected individuals is unknown. To address this question, chimpanzees with persistent HCV infection were treated with anti-PD-1 antibodies. A significant reduction in HCV viremia was observed in one of three treated animals without apparent hepatocellular injury. Viremia rebounded in the responder animal when antibody treatment was discontinued. Control of HCV replication was associated with restoration of intrahepatic CD4+ and CD8+ T-cell immunity against multiple HCV proteins. The responder animal had a history of broader T-cell immunity to multiple HCV proteins than the two chimpanzees that did not respond to PD-1 therapy. The results suggest that successful PD-1 blockade likely requires a critical threshold of preexisting virus-specific T cells in liver and warrants consideration of therapeutic vaccination strategies in combination with PD-1 blockade to broaden narrow responses. Anti-PD-1 immunotherapy may also facilitate control of other persistent viruses, notably the hepatitis B virus where options for long-term control of virus replication are limited. PMID:23980172

  17. Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice

    PubMed Central

    Frebel, Helge; Nindl, Veronika; Schuepbach, Reto A.; Braunschweiler, Thomas; Richter, Kirsten; Vogel, Johannes; Wagner, Carsten A.; Loffing-Cueni, Dominique; Kurrer, Michael; Ludewig, Burkhard

    2012-01-01

    The inhibitory programmed death 1 (PD-1)–programmed death ligand 1 (PD-L1) pathway contributes to the functional down-regulation of T cell responses during persistent systemic and local virus infections. The blockade of PD-1–PD-L1–mediated inhibition is considered as a therapeutic approach to reinvigorate antiviral T cell responses. Yet previous studies reported that PD-L1–deficient mice develop fatal pathology during early systemic lymphocytic choriomeningitis virus (LCMV) infection, suggesting a host protective role of T cell down-regulation. As the exact mechanisms of pathology development remained unclear, we set out to delineate in detail the underlying pathogenesis. Mice deficient in PD-1–PD-L1 signaling or lacking PD-1 signaling in CD8 T cells succumbed to fatal CD8 T cell–mediated immunopathology early after systemic LCMV infection. In the absence of regulation via PD-1, CD8 T cells killed infected vascular endothelial cells via perforin-mediated cytolysis, thereby severely compromising vascular integrity. This resulted in systemic vascular leakage and a consequential collapse of the circulatory system. Our results indicate that the PD-1–PD-L1 pathway protects the vascular system from severe CD8 T cell–mediated damage during early systemic LCMV infection, highlighting a pivotal physiological role of T cell down-regulation and suggesting the potential development of immunopathological side effects when interfering with the PD-1–PD-L1 pathway during systemic virus infections. PMID:23230000

  18. Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+ T-Cell Proliferative Capacity

    PubMed Central

    Braun, Nicole A.; Celada, Lindsay J.; Herazo-Maya, Jose D.; Abraham, Susamma; Shaginurova, Guzel; Sevin, Carla M.; Grutters, Jan; Culver, Daniel A.; Dworski, Ryszard; Sheller, James; Massion, Pierre P.; Polosukhin, Vasiliy V.; Johnson, Joyce E.; Kaminski, Naftali; Wilkes, David S.; Oswald-Richter, Kyra A.

    2014-01-01

    Rationale: Effective therapeutic interventions for chronic, idiopathic lung diseases remain elusive. Normalized T-cell function is an important contributor to spontaneous resolution of pulmonary sarcoidosis. Up-regulation of inhibitor receptors, such as programmed death-1 (PD-1) and its ligand, PD-L1, are important inhibitors of T-cell function. Objectives: To determine the effects of PD-1 pathway blockade on sarcoidosis CD4+ T-cell proliferative capacity. Methods: Gene expression profiles of sarcoidosis and healthy control peripheral blood mononuclear cells were analyzed at baseline and follow-up. Flow cytometry was used to measure ex vivo expression of PD-1 and PD-L1 on systemic and bronchoalveolar lavage–derived cells of subjects with sarcoidosis and control subjects, as well as the effects of PD-1 pathway blockade on cellular proliferation after T-cell receptor stimulation. Immunohistochemistry analysis for PD-1/PD-L1 expression was conducted on sarcoidosis, malignant, and healthy control lung specimens. Measurements and Main Results: Microarray analysis demonstrates longitudinal increase in PDCD1 gene expression in sarcoidosis peripheral blood mononuclear cells. Immunohistochemistry analysis revealed increased PD-L1 expression within sarcoidosis granulomas and lung malignancy, but this was absent in healthy lungs. Increased numbers of sarcoidosis PD-1+ CD4+ T cells are present systemically, compared with healthy control subjects (P < 0.0001). Lymphocytes with reduced proliferative capacity exhibited increased proliferation with PD-1 pathway blockade. Longitudinal analysis of subjects with sarcoidosis revealed reduced PD-1+ CD4+ T cells with spontaneous clinical resolution but not with disease progression. Conclusions: Analogous to the effects in other chronic lung diseases, these findings demonstrate that the PD-1 pathway is an important contributor to sarcoidosis CD4+ T-cell proliferative capacity and clinical outcome. Blockade of the PD-1 pathway may be a

  19. Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells.

    PubMed

    Akiyama, Yasuto; Nonomura, Chizu; Kondou, Ryota; Miyata, Haruo; Ashizawa, Tadashi; Maeda, Chie; Mitsuya, Koichi; Hayashi, Nakamasa; Nakasu, Yoko; Yamaguchi, Ken

    2016-09-01

    Immune checkpoint antibody-mediated blockade has gained attention as a new cancer immunotherapy strategy. Accumulating evidence suggests that this therapy imparts a survival benefit to metastatic melanoma and non-small cell lung cancer patients. A substantial amount of data on immune checkpoint antibodies has been collected from clinical trials; however, the direct effect of the antibodies on human peripheral blood mononuclear cells (PBMCs) has not been exclusively investigated. In this study, we developed an anti-programmed death-1 (PD-1) antibody (with biosimilarity to nivolumab) and examined the effects of the antibody on PBMCs derived from cancer patients. Specifically, we investigated the effects of the anti-PD-1 antibody on proliferation, cytokine production, cytotoxic T lymphocytes (CTL) and regulatory T cells. These investigations yielded several important results. First, the anti-PD-1 antibody had no obvious effect on resting PBMCs; however, high levels of the anti-PD-1 antibody partly stimulated PBMC proliferation when accompanied by an anti-CD3 antibody. Second, the anti-PD-1 antibody restored the growth inhibition of anti-CD3 Ab-stimulated PBMCs mediated by PD-L1. Third, the anti-PD-1 antibody exhibited a moderate inhibitory effect on the induction of myeloid-derived suppressor cells (MDSCs) by anti-CD3 antibody stimulation. Additionally, the presence of the anti-PD-1 antibody promoted antigen-specific CTL induction, which suggests that combining anti-PD-1 antibody and conventional immunotherapy treatments may have beneficial effects. These results indicate that specific cellular immunological mechanisms are partly responsible for the antitumor effect exhibited by the anti-PD-1 antibody against advanced cancers in clinical trials. PMID:27573705

  20. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2

    PubMed Central

    Takamatsu, Masako; Kobayashi-Imanishi, Wakana; Hashimoto-Tane, Akiko; Azuma, Miyuki

    2012-01-01

    Programmed cell death 1 (PD-1) is a negative costimulatory receptor critical for the suppression of T cell activation in vitro and in vivo. Single cell imaging elucidated a molecular mechanism of PD-1–mediated suppression. PD-1 becomes clustered with T cell receptors (TCRs) upon binding to its ligand PD-L1 and is transiently associated with the phosphatase SHP2 (Src homology 2 domain–containing tyrosine phosphatase 2). These negative costimulatory microclusters induce the dephosphorylation of the proximal TCR signaling molecules. This results in the suppression of T cell activation and blockade of the TCR-induced stop signal. In addition to PD-1 clustering, PD-1–TCR colocalization within microclusters is required for efficient PD-1–mediated suppression. This inhibitory mechanism also functions in PD-1hi T cells generated in vivo and can be overridden by a neutralizing anti–PD-L1 antibody. Therefore, PD-1 microcluster formation is important for regulation of T cell activation. PMID:22641383

  1. Association of programmed death-1 gene polymorphism rs2227981 with tumor: evidence from a meta analysis

    PubMed Central

    Mamat, Umarjan; Arkinjan, Muyassar

    2015-01-01

    To investigate the association of programmed death-1 gene polymorphism rs2227981 with tumor risk. The PubMed, Medline, Ovid Medline, EMBASE, Web of Knowledge were searched. Meta-analyses were conducted using RevMan 5.2.2 software. Total six researches involving in a total of 1427 tumor patients and 1811 healthy control people were included into this meta analysis. There was no association of PD-1 gene polymorphism with total tumor risk under four genetic models. (CT+TT vs CC, OR=1.09, 95% CI=0.80-1.49, P=0.59; CT+CC vs TT, OR=0.93, 95% CI=0.52-1.66, P=0.61; TT vs CC, OR=0.99, 95% CI=0.57-1.72, P=0.97; CT vs CC, OR=1.16, 95% CI=0.80-1.70, P=0.43). The sub-group analysis shown there were a significantly difference on association of PD-1 gene polymorphism with digestive system tumor risk between tumor patients and healthy control people, except recessive model. (CT+TT vs CC, OR=1.57, 95% CI=1.20-2.07, P=0.001; TT vs CC, OR=1.67, 95% CI=1.12-2.49, P=0.01; CT vs CC, OR=1.51, 95% CI=1.13-2.01, P=0.005). Moreover, the meta analysis results shown that there were association of PD-1 gene polymorphism with tumor risk under two models for the tumor specific occurring only in women. (CT+TT vs CC, OR=0.80, 95% CI=0.67-0.95, P=0.01; TT vs CC, OR=0.61, 95% CI=0.44-0.83, P=0.002). This study suggests that PD-1 gene polymorphism rs2227981 is associated with specific tumor types, including digestive system tumor and tumor specific occurring in woman. PMID:26550254

  2. Results of clinical trials with anti-programmed death 1/programmed death ligand 1 inhibitors in lung cancer

    PubMed Central

    González-Cao, María; Barrón, Feliciano; Riso, Aldo; Rosell, Rafael

    2015-01-01

    One of the main hallmarks of cancer is the capability of evading immune destruction. In order to drive tumor progression, malignant cells are able to promote immunosuppressive mechanisms avoiding recognition and elimination. Increasing knowledge of the mechanisms of immune tolerance has led to the identification of several membrane receptors strongly implicated in this cancer feature: the immune checkpoints. Among them, programmed death 1 (PD-1) receptors and their ligands have been identified as potential targets for a new anti-cancer therapeutic approach: the use of immune-modulatory monoclonal antibodies designed to interrupt the immune escape activated by the interaction of PD-1 receptors and their ligands. Five of these antibodies are now in their late stages of clinical development and this review will summarize their up-to-date efficacy and toxicity data. PMID:26798585

  3. Predictive factors of activity of anti-programmed death-1/programmed death ligand-1 drugs: immunohistochemistry analysis

    PubMed Central

    Chakravarti, Nitin

    2015-01-01

    Anti-programmed death-1 (anti-PD1)/programmed death ligand-1 (PD-L1) therapeutic antibodies targeting regulatory pathways in T cells have recently shown to promising clinical effectiveness in several solid tumors by enhancing antitumor immune response. Immune checkpoint therapy has propelled therapeutic efforts opening a new field in cancer treatment. However, durable clinical response has been educed only in a fraction of patients, underlining the need to predictively select those patients most likely to respond, e.g., by detecting predictive biomarkers. Immunohistochemistry (IHC) detection of PD-L1 in tumor cells has been used in various trials of anti-PD-1/PD-L1 agents to try to select those patients most likely to respond. However, since there are different techniques and scoring systems, results have not been conclusive. Thus efforts are needed to develop standardized IHC assays as well as to explore additional biomarkers to evaluate and predict immune responses elicited by anti-PD-1/PD-L1 therapies. PMID:26798583

  4. Implications of Programmed Cell Death 1 Ligand 1 Heterogeneity in the Selection of Patients With Non-Small Cell Lung Cancer to Receive Immunotherapy.

    PubMed

    Mansfield, A S; Dong, H

    2016-09-01

    The use of programmed cell death 1 ligand 1 (PD-L1) as a predictive biomarker to select patients to receive programmed cell death 1 (PD-1) or PD-L1 inhibitors in non-small cell lung cancer (NSCLC) is limited by the definitions of positivity, interassay agreement, and intra- and intertumoral heterogeneity of expression. Although PD-L1 expression enriches for responses, the lack of expression does not exclude clinical benefit. PMID:26916808

  5. Negative influence of programmed death-1-ligands on the survival of esophageal cancer patients treated with chemotherapy.

    PubMed

    Tanaka, Koji; Miyata, Hiroshi; Sugimura, Keijiro; Kanemura, Takashi; Hamada-Uematsu, Mika; Mizote, Yu; Yamasaki, Makoto; Wada, Hisashi; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro; Tahara, Hideaki

    2016-06-01

    The programmed death-1/programmed death-1 ligands (PD-1/PD-L) pathway plays an important role in immunological tumor evasion. However, the clinical significance of the PD-L (L1 and L2) expression in esophageal cancer treated with chemotherapy has not been fully investigated. We examined the expression of PD-L of the primary tumors obtained from 180 esophageal cancer patients who underwent radical resection with or without neoadjuvant chemotherapy (NAC) using immunohistochemical staining. The relationship between the expression patterns and clinico-pathological characteristics was examined. In the present study, 53 patients (29.4%) and 88 patients (48.3%) were classified into positive for PD-L1 and PD-L2 expression, respectively. In all the patients examined, overall survival rates of the patients with tumors positive for PD-L1 or PD-L2 were significantly worse than those with tumors negative for PD-L1 or PD-L2 (P = 0.0010 and P = 0.0237, respectively). However, subgroup analysis showed that these tendencies are only found in the patients treated with NAC, and not in those without NAC. The patients with positive PD-L1 expression had a significantly higher rate of NAC history (P = 0.0139), but those with positive PD-L2 expression did not have a significantly high rate of NAC history (P = 0.6127). There is no significant relationship between PD-L1 expression and response to chemotherapy (P = 0.3118), but patients with positive PD-L2 expression had significantly inferior responses to chemotherapy (P = 0.0034). The PD-1/PD-L pathway might be an immunological mechanism associated with the long-term effectiveness of chemotherapy in esophageal cancer patients. Further investigation into the roles of PD-1 pathway in chemotherapy could lead to the development of better treatment options for this disease. PMID:27015293

  6. Programmed death 1 and B and T lymphocyte attenuator immunoreceptors and their association with malignant T-lymphoproliferative disorders: brief review.

    PubMed

    Karakatsanis, Stamatis; Bertsias, George; Roussou, Paraskevi; Boumpas, Dimitrios

    2014-09-01

    Malignant T-cell lymphoproliferative diseases are relatively rare. T cells are activated through the T-cell receptor with the aid of costimulating molecules that can be either excitatory or inhibitory. Such pathways have been also implicated in mechanisms of malignant T-cell lymphoproliferative diseases' persistence and relapse by circumventing immune responses. To date, three major immunoinhibitory molecules have been recognized, namely programmed cell death-1 (PD-1), B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although CTLA-4 is considered the 'gatekeeper' of immune tolerance, PD-1 negatively regulates immune responses broadly, whereas BTLA activation has been shown to inhibit CD8+ cancer-specific T cells. Both PD-1 and BTLA downregulate proximal T-cell receptor signalling cascade and are involved in immune evasion of leukaemias and lymphomas, even after allogeneic stem cell transplantation. These immunoregulatory molecules can have seemingly a synergistic effect on weakening the immune response of patients with haematological malignancies, and their manipulation represents a very active field of preclinical as well as clinical interest. PMID:24038528

  7. Surgical trauma induces postoperative T-cell dysfunction in lung cancer patients through the programmed death-1 pathway.

    PubMed

    Xu, Pingbo; Zhang, Ping; Sun, Zhirong; Wang, Yun; Chen, Jiawei; Miao, Changhong

    2015-11-01

    The programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) pathway have been shown to be involved in tumor-induced and sepsis-induced immunosuppression. However, whether this pathway is involved in the surgery-induced dysfunction of T lymphocytes is not known. Here, we analyzed expression of PD-1 and PD-L1 on human peripheral mononuclear cells during the perioperative period. We found that surgery increased PD-1/PD-L1 expression on immune cells, which was correlated with the severity of surgical trauma. The count of T lymphocytes and natural killer cells reduced after surgery, probably due to the increased activity of caspase-3. Caspase-3 level was positively correlated with PD-1 expression. Profile of perioperative cytokines and hormones in plasma showed a significantly increased level of interferon-α, as well as various inflammatory cytokines and stress hormones. In ex vivo experiments, administration of anti-PD-1 antibody significantly ameliorated T-cell proliferation and partially reversed the T-cell apoptosis induced by surgical trauma. We provide evidences that surgical trauma can induce immunosuppression through the PD-1/PD-L1 pathway. This pathway could be a target for preventing postoperative cellular immunosuppression. PMID:26183035

  8. T-bet regulates differentiation of forkhead box protein 3+ regulatory T cells in programmed cell death-1-deficient mice.

    PubMed

    Tahara, M; Kondo, Y; Yokosawa, M; Tsuboi, H; Takahashi, S; Shibayama, S; Matsumoto, I; Sumida, T

    2015-02-01

    Programmed cell death-1 (PD-1) plays an important role in peripheral T cell tolerance, but whether or not it affects the differentiation of helper T cell subsets remains elusive. Here we describe the importance of PD-1 in the control of T helper type 1 (Th1) cell activation and development of forkhead box protein 3 (FoxP3(+)) regulatory T cells (Tr(egs)). PD-1-deficient T cell-specific T-bet transgenic (P/T) mice showed growth retardation, and the majority died within 10 weeks. P/T mice showed T-bet over-expression, increased interferon (IFN)-γ production by CD4(+) T cells and significantly low FoxP3(+) T(reg) cell percentage. P/T mice developed systemic inflammation, which was probably induced by augmented Th1 response and low FoxP3(+) T(reg) count. The study identified a unique, previously undescribed role for PD-1 in Th1 and T(reg) differentiation, with potential implication in the development of Th1 cell-targeted therapy. PMID:25219397

  9. Attenuation of the programmed cell death-1 pathway increases the M1 polarization of macrophages induced by zymosan

    PubMed Central

    Chen, W; Wang, J; Jia, L; Liu, J; Tian, Y

    2016-01-01

    Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals on interaction with its 2 ligands, PD-L1 and PD-L2. We assessed the contribution of the PD-1 pathway to regulating the polarization of macrophages that promote inflammation induced by zymosan. We found that PD-1−/− mice developed robust peritonitis with more abundant infiltration of M1 macrophages, accompanied by higher levels of pro-inflammation factors, especially monocyte chemotactic protein-1 (MCP-1) compared with wild-type controls ex vivo and in vitro. Our results indicated that PD-1 deficiency promotes M1 rather than M2 polarization of macrophages by enhancing the expression of p-STAT1/p-NF-κB p65 and downregulating p-STAT6. We found that PD-1 engagement followed by zymosan stimulation might primarily attenuate the phosphorylation of tyrosine residue in PD-1 receptor/ligand and the recruitment of SHP-2 to PD-1 receptor/ligand, leading to the reduction of M1 type cytokine production. PMID:26913605

  10. Crystal Structure of the Complex Between Programmed Death-1 (PD-1) and its Ligand PD-L2

    SciTech Connect

    Lazar-Molnar,E.; Yan, Q.; Cao, E.; Ramagopal, U.; Nathenson, S.; Almo, S.

    2008-01-01

    Programmed death-1 (PD-1) is a member of the CD28/B7 superfamily that delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. The high-resolution crystal structure of the complex formed by the complete ectodomains of murine PD-1 and PD-L2 revealed a 1:1 receptor:ligand stoichiometry and displayed a binding interface and overall molecular organization distinct from that observed in the CTLA-4/B7 inhibitory complexes. Furthermore, our structure also provides insights into the association between PD-1 and PD-L1 and highlights differences in the interfaces formed by the two PD-1 ligands (PD-Ls) Mutagenesis studies confirmed the details of the proposed PD-1/PD-L binding interfaces and allowed for the design of a mutant PD-1 receptor with enhanced affinity. These studies define spatial and organizational constraints that control the localization and signaling of PD-1/PD-L complexes within the immunological synapse and provide a basis for manipulating the PD-1 pathways for immunotherapy.

  11. Programmed cell death-1 is expressed in large retinal ganglion cells and is upregulated after optic nerve crush.

    PubMed

    Wang, Wei; Chan, Ann; Qin, Yu; Kwong, Jacky M K; Caprioli, Joseph; Levinson, Ralph; Chen, Ling; Gordon, Lynn K

    2015-11-01

    Programmed cell death-1 (PD-1) is a key negative receptor inducibly expressed on T cells, B cells and dendritic cells. It was discovered on T cells undergoing classical programmed cell death. Studies showed that PD-1 ligation promotes retinal ganglion cell (RGC) death during retinal development. The purpose of this present study is to characterize PD-1 regulation in the retina after optic nerve crush (ONC). C57BL/6 mice were subjected to ONC and RGC loss was monitored by immunolabelling with RNA-binding protein with multiple splicing (Rbpms). Time course of PD-1 mRNA expression was determined by real-time PCR. PD-1 expression was detected with anti-PD-1 antibody on whole mount retinas. PD-1 staining intensity was quantitated. Colocalization of PD-1 and cleaved-caspase-3 after ONC was analyzed. Real-time PCR results demonstrated that PD-1 gene expression was significantly upregulated at day 1, 3, 7, 10 and 14 after ONC. Immunofluorescent staining revealed a dramatic increase of PD-1 expression following ONC. In both control and injured retinas, PD-1 tended to be up-expressed in a subtype of RGCs, whose somata size were significantly larger than others. Compared to control, PD-1 intensity in large RGCs was increased by 82% in the injured retina. None of the large RGCs expressed cleaved-caspase-3 at day 5 after ONC. Our work presents the first evidence of PD-1 induction in RGCs after ONC. This observation supports further investigation into the role of PD-1 expression during RGC death or survival following injury. PMID:26277582

  12. Programmed cell death 1 inhibits inflammatory helper T-cell development through controlling the innate immune response.

    PubMed

    Rui, Yuxiang; Honjo, Tasuku; Chikuma, Shunsuke

    2013-10-01

    Programmed cell death 1 (PD-1) is an inhibitory coreceptor on immune cells and is essential for self-tolerance because mice genetically lacking PD-1 (PD-1(-/-)) develop spontaneous autoimmune diseases. PD-1(-/-) mice are also susceptible to severe experimental autoimmune encephalomyelitis (EAE), characterized by a massive production of effector/memory T cells against myelin autoantigen, the mechanism of which is not fully understood. We found that an increased primary response of PD-1(-/-) mice to heat-killed mycobacteria (HKMTB), an adjuvant for EAE, contributed to the enhanced production of T-helper 17 (Th17) cells. Splenocytes from HKMTB-immunized, lymphocyte-deficient PD-1(-/-) recombination activating gene (RAG)2(-/-) mice were found to drive antigen-specific Th17 cell differentiation more efficiently than splenocytes from HKMTB-immunized PD-1(+/+) RAG2(-/-) mice. This result suggested PD-1's involvement in the regulation of innate immune responses. Mice reconstituted with PD-1(-/-) RAG2(-/-) bone marrow and PD-1(+/+) CD4(+) T cells developed more severe EAE compared with the ones reconstituted with PD-1(+/+) RAG2(-/-) bone marrow and PD-1(+/+) CD4(+) T cells. We found that upon recognition of HKMTB, CD11b(+) macrophages from PD-1(-/-) mice produced very high levels of IL-6, which helped promote naive CD4(+) T-cell differentiation into IL-17-producing cells. We propose a model in which PD-1 negatively regulates antimycobacterial responses by suppressing innate immune cells, which in turn prevents autoreactive T-cell priming and differentiation to inflammatory effector T cells. PMID:24043779

  13. Programmed death-1 pathway in host tissues ameliorates Th17/Th1-mediated experimental chronic graft-versus-host disease.

    PubMed

    Fujiwara, Hideaki; Maeda, Yoshinobu; Kobayashi, Koichiro; Nishimori, Hisakazu; Matsuoka, Ken-Ichi; Fujii, Nobuharu; Kondo, Eisei; Tanaka, Takehiro; Chen, Lieping; Azuma, Miyuki; Yagita, Hideo; Tanimoto, Mitsune

    2014-09-01

    Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the role of the programmed death-1 (PD-1) pathway in chronic GVHD using a well-defined mouse model of B10.D2 (H-2(d)) donor to BALB/c (H-2(d)) recipients. PD-1 expression on allogeneic donor T cells was upregulated continuously in chronic GVHD development, whereas PD-L1 expression in host tissues was transiently upregulated and declined to basal levels in the late posttransplant period. Blockade of the PD-1 pathway by anti-PD-1, anti-PD-L1, or anti-PD-L2 mAbs exacerbated clinical and pathologic chronic GVHD. Chimeric mice revealed that PD-L1 expression in host tissues suppressed expansion of IL-17(+)IFN-γ(+) T cells, and that PD-L1 expression on hematopoietic cells plays a role in the development of regulatory T cells only during the early transplantation period but does not affect the severity of chronic GVHD. Administration of the synthetic retinoid Am80 overcame the IL-17(+)IFN-γ(+) T cell expansion caused by PD-L1 deficiency, resulting in reduced chronic GVHD damage in PD-L1(-/-) recipients. Stimulation of the PD-1 pathway also alleviated chronic GVHD. These results suggest that the PD-1 pathway contributes to the suppression of Th17/Th1-mediated chronic GVHD and may represent a new target for the prevention or treatment of chronic GVHD. PMID:25080485

  14. Programmed Cell Death-1 Polymorphisms Decrease the Cancer Risk: A Meta-Analysis Involving Twelve Case-Control Studies

    PubMed Central

    Dong, Wenjing; Gong, Mancheng; Shi, Zhirong; Xiao, Jianjun; Zhang, Junkai; Peng, Jiewen

    2016-01-01

    Programmed cell death-1 (PD-1) plays an important inhibitory role in anti-tumor responses, so it is considered as a powerful candidate gene for individual’s genetic susceptibility to cancer. Recently, some epidemiological studies have evaluated the association between PD-1 polymorphisms and cancer risk. However, the results of the studies are conflicting. Therefore, a meta-analysis was performed. We identified all studies reporting the relationship between PD-1 polymorphisms and cancers by electronically searches. According to the inclusion criteria and the quality assessment of Newcastle-Ottawa Scale (NOS), only high quality studies were included. A total of twelve relevant studies involving 5,206 cases and 5,174 controls were recruited. For PD-1.5 (rs2227981) polymorphism, significantly decreased cancer risks were obtained among overall population, Asians subgroup and population-based subgroup both in TT vs. CC and TT vs. CT+CC genetic models. In addition, a similar result was also found in T vs. C allele for overall population. However, there were no significant associations between either PD-1.9 (rs2227982) or PD-1 rs7421861 polymorphisms and cancer risks in all genetic models and alleles. For PD-1.3 (rs11568821) polymorphism, we found different cancer susceptibilities between GA vs. GG and AA vs. AG+GG genetic models, and no associations between AA vs. GG, AA+AG vs. GG genetic models or A vs. G allele and cancer risks. In general, our results firstly indicated that PD-1.5 (rs2227981) polymorphism is associated a strongly decreased risk of cancers. Additional epidemiological studies are needed to confirm our findings. PMID:27031235

  15. Programmed Death 1 (PD-1) is involved in the development of proliferative diabetic retinopathy by mediating activation-induced apoptosis

    PubMed Central

    Fang, Mengyuan; Meng, Qianli; Wang, Liya; Zhao, Zhaoxia; Zhang, Liang; Kuang, Jian; Cui, Ying; Mai, Liping; Zhu, Jiening

    2015-01-01

    Purpose Recent studies revealed that immunological mechanisms play a prominent role in the pathogenesis of proliferative diabetic retinopathy (PDR). Given the importance of the immune response in PDR and the significance of the programmed death 1 (PD-1) pathway as an immune regulatory pathway, the aim of this study is to determine the expression and functional characteristics of the PD-1 pathway in peripheral blood lymphocytes from patients with PDR. Methods Peripheral blood lymphocytes were obtained from patients with PDR, age-matched patients with diabetes mellitus and no diabetic retinopathy (DM-NDR), and controls. The mRNA expression of PD-1 and its ligands were determined using real-time PCR. The frequencies of PD-1 and its ligands, activation-induced apoptosis, IFN-γ, and IL-4 were determined by flow cytometry. Results The PD-1 mRNA expression markedly decreased, while the frequency of PD-1+ cells increased in the PDR group compared with the DM-NDR and control groups. The expression of PD-ligand 1 (PD-L1) mRNA and PD-L1+ cells in the PDR group was lower than that in the other two groups. In the PDR group, the frequency of Annexin V+PI- and Annexin V+PI-PD-1+ cells increased, while the frequency of Annexin V+PI-PD-L1+ cells decreased. Although their expression was upregulated, the ratio of PD-1+ IFN-γ+ to PD-1+IL-4+ cells in the PDR group was not significantly different to that in the DM-NDR and control groups. Conclusions These results suggest that PD-1 is involved in the development of PDR by mediating activation-induced apoptosis. PMID:26321864

  16. Programmed death-1 (PD-1) rs2227981 C > T polymorphism is associated with cancer susceptibility: a meta-analysis

    PubMed Central

    Tang, Weifeng; Wang, Yafeng; Jiang, Heping; Liu, Pinghua; Liu, Chao; Gu, Haiyong; Chen, Shuchen; Kang, Mingqiang

    2015-01-01

    Several studies have focused on the correlation between the programmed death-1 (PD-1) rs2227981 C > T polymorphism and the risk of cancer; however, the results of such studies remain conflicting. To address this gap, we performed this meta-analysis to identify the potential association. Search strategies were performed in PubMed and EMBASE using appropriate terms. In total, 2,977 cancer cases and 2,642 controls from seven publications were recruited in our study. According to the seven eligible publications, the odds ratios (ORs) and 95% confidence intervals (CIs) on the risk of cancer for the TT vs. CC and TT vs. CT+CC genotypes were 0.67 and 0.50-0.91 and 0.65 and 0.47-0.90, respectively. In a subgroup analysis by cancer type, PD-1 rs2227981 C > T polymorphism was associated with a significantly decreased risk of breast cancer (OR, 0.82; 95% CI, 0.71-0.95; P = 0.009 for T vs. C and OR, 0.76; 95% CI, 0.63-0.92; P = 0.005 for TT+CT vs. CC) and of other cancer (OR, 0.58; 95% CI, 0.36-0.92; P = 0.004 for TT vs. CT+CC). In a subgroup analysis by ethnicity, a significant decreased cancer risk was identified among Asians (OR, 0.74; 95% CI, 0.63-0.86; P < 0.001 for T vs. C and OR, 0.71; 95% CI, 0.59-0.87; P = 0.001 for TT+CT vs. CC) and among Caucasians (OR, 0.66; 95% CI, 0.44-0.99; P = 0.047 for TT vs. CT+CC). These findings highlight the fact that the T allele of PD-1 rs2227981 C > T polymorphism modestly decreases the susceptibility of cancer. Nevertheless, further large and well-designed studies are needed to enrich the evidence of this association. PMID:26885204

  17. Programmed death-1 ligand 1 and 2 are highly expressed in pleomorphic carcinomas of the lung: Comparison of sarcomatous and carcinomatous areas.

    PubMed

    Kim, Sehui; Kim, Moon-Young; Koh, Jaemoon; Go, Heounjeong; Lee, Dong Soo; Jeon, Yoon Kyung; Chung, Doo Hyun

    2015-11-01

    Pleomorphic carcinoma (PC) of the lung is a rare type of poorly differentiated non-small cell lung carcinoma (NSCLC) that belongs to sarcomatoid carcinoma (SC). It exhibits aggressive behaviour and resistance to chemotherapy and radiotherapy. Recently, immunotherapy targeting the programmed death-1 (PD-1)/PD ligand 1 (PD-L1) pathway has demonstrated favourable clinical outcomes in NSCLC. However, the expression patterns of PD-1-related molecules in pulmonary PC remain elusive. PD-L1 and PD-L2 expression was estimated in 41 cases of PC using immunohistochemistry. CD8(+) and PD-1(+) tumour-infiltrating lymphocytes (TILs) were also evaluated. PD-L1 and PD-L2 were highly expressed in pulmonary PCs (90.2% [37/41)]; 87.8% [36/41]). The amount of CD8(+) or PD-1(+) TILs and the ratio of PD-1(+)/CD8(+) TILs in PC were higher in males, smokers and older patients. PD-L1-positive PCs were infiltrated by higher numbers of CD8(+) TILs compared to PD-L1-negative cases (P=0.006). Of note, PD-L1 expression in pulmonary PCs was significantly higher in sarcomatous areas than in the carcinomatous portion (P=0.006). PC patients with a high ratio of PD-1(+)/CD8(+) TILs showed a shorter progression-free survival (P=0.036), whereas PD-L1 and PD-L2 expression had no prognostic implications. Our study demonstrates that pulmonary PCs very frequently express PD-L1 and PD-L2. Moreover, their expression is higher in sarcomatous cells than in carcinomatous areas. Thus, targeting the PD-1/PD-L1 pathway may represent a potential therapeutic candidate for this aggressive tumour. PMID:26329973

  18. Expression of programmed death 1 ligand 1 on periodontal tissue cells as a possible protective feedback mechanism against periodontal tissue destruction

    PubMed Central

    ZHANG, JIEHUA; WANG, CHIEH-MEI; ZHANG, PING; WANG, XIAOQIAN; CHEN, JIAO; YANG, JUN; LU, WANLU; ZHOU, WENJIE; YUAN, WENWEN; FENG, YUN

    2016-01-01

    Programmed death 1 ligand 1 (PD-L1) is a negative co-stimulatory molecule in immune responses. Previous reports have indicated that inflammatory cytokines can upregulate the expression of PD-L1 in tumor cells, which in turn suppresses host immune responses. Periodontitis is characterized by persistent inflammation of the periodontium, which is initiated by infection with oral bacteria and results in damage to cells and the matrices of the periodontal connective tissues. In the present study, the expression and function of PD-L1 in periodontal tissue destruction were examined. Periodontal ligament cells (PDLCs) were stimulated by inflammatory cytokines and periodontal pathogens. The expression and function of PD-L1 on the surface of PDLCs was investigated using flow cytometry in vitro. Periodontal disease was induced by the injection of Porphyromonas gingivalis in mouse models. The expression levels of PD-L1 in the periodontal tissues of the mice were analyzed using flow cytometry and immunohistochemistry. PD-L1 was inducibly expressed on the PDLCs by the inflammatory cytokines and periodontal pathogens. The inflammation-induced expression of PD-L1 was shown to cause the apoptosis of activated T lymphocytes and improve the survival of PDLCs. Furthermore, in the mouse model of experimental periodontitis, the expression of PD-L1 in severe cases of periodontitis was significantly lower, compared with that in mild cases. By contrast, no significant differences were observed between the healthy control and severe periodontitis groups. The results of the present study showed that the expression of PD-L1 may inhibit the destruction of periodontal tissues, indicating the involvement of a possible protective feedback mechanism against periodontal infection. PMID:26847035

  19. Variable patterns of programmed death-1 expression on fully functional memory T cells after spontaneous resolution of hepatitis C virus infection.

    PubMed

    Bowen, David G; Shoukry, Naglaa H; Grakoui, Arash; Fuller, Michael J; Cawthon, Andrew G; Dong, Christine; Hasselschwert, Dana L; Brasky, Kathleen M; Freeman, Gordon J; Seth, Nilufer P; Wucherpfennig, Kai W; Houghton, Michael; Walker, Christopher M

    2008-05-01

    The inhibitory receptor programmed death-1 (PD-1) is present on CD8(+) T cells in chronic hepatitis C virus (HCV), but expression patterns in spontaneously resolving infections are incompletely characterized. Here we report that PD-1 was usually absent on memory CD8(+) T cells from chimpanzees with resolved infections, but sustained low-level expression was sometimes observed in the absence of apparent virus replication. PD-1-positive memory T cells expanded and displayed antiviral activity upon reinfection with HCV, indicating conserved function. This animal model should facilitate studies of whether PD-1 differentially influences effector and memory T-cell function in resolved versus persistent human infections. PMID:18337576

  20. Programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma.

    PubMed

    Paydas, Semra; Bağır, Emine; Seydaoglu, Gulsah; Ercolak, Vehbi; Ergin, Melek

    2015-09-01

    Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are new targets in cancer immunotherapy. PD-1 protein is an immune checkpoint expressed in many tumors. Epstein-Barr virus (EBV) is present in malignant Hodgkin/Reed-Sternberg (HRS) cells in approximately 40-50 % of Hodgkin lymphoma (HL). The aim of this study is to evaluate the clinical and prognostic importance of PD-1 and/or PD-L1 in HL and also to determine the association between EBV-encoded RNA (EBER) and PD-1/PD-L1. Formalin-fixed, paraffin-embedded tissue samples from 87 cases with HL were analyzed in this study. Immunohistochemical staining was performed to detect the PD-1 and PD-L1 expressions. Chromogenic in situ hybridization for EBER was performed using fluorescein-labeled oligonucleotide probes. PD-1 and PD-L1 expressions were found in 20 % of the cases. The EBER positivity was found in 40 cases (45 %). It has been found that co-expression of PD-1 and PD-L1 was associated with shorter survival although PD-1 or PD-L1 expressions were not found to be related with survival. Overall survival (OS) and disease-free survival (DFS) in cases without PD-1 and PD-L1 expressions were 135 and 107 months, respectively. OS and DFS in cases with co-expression for PD-1 and PD-L1 were 24 and 20 months, respectively, and these differences were found to be statistically significant for both OS and DFS (p = 0.002 and p = 0.003, respectively). Cox regression analysis showed that co-expression of PD-1 and PD-L1 was found to be an independent risk factor for prognosis (OR 6.9, 95 % CI 1.9-24.3). Targeting PD-1 and/or PD-L1 is meaningful due to the 20 % expression of each in HL, and we did not find an important association between PD-1 and PD-L1 and EBER expression in HL. Very poor outcome in cases with co-expression of PD-1/PD-L1 suggests new avenues to detect the new prognostic markers and also therapeutic approaches in HL. PMID:26004934

  1. Programmed death 1 expression in the peritumoral microenvironment is associated with a poorer prognosis in classical Hodgkin lymphoma.

    PubMed

    Koh, Young Wha; Jeon, Yoon Kyung; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

    2016-06-01

    Programmed cell death protein-1 (PD-1) inhibitor may be therapeutic in patients with relapsed or refractory classical Hodgkin's lymphoma (cHL). This study examined the prognostic significance of PD-1 and two PD-1 ligands (PD-L1 and PD-L2) in uniformly treated cHL. Diagnostic tissues from 109 cHL patients treated with a doxorubicin, bleomycin, vinblastine, and dacarbazine regimen were evaluated retrospectively by immunohistochemical analysis of PD-L1, PD-L2, and PD-1 expressions. The median follow-up time was 4.91 years (range, 0.17-17.33 years). Thirteen patients (11 %) expressed PD-1 protein in the peritumoral microenvironment, which was associated with poor overall survival (OS) (P = 0.017). PD-L1 or PD-L2 expression was not associated with OS. There was no correlation between PD-L1 and PD-1 expression or between PD-L2 and PD-1 expression. Multivariate analysis identified PD-1 protein as an independent prognostic factor for OS (P = 0.019). Subgroup analysis according to the Ann Arbor stage of cHL showed that PD-1 protein expression had a prognostic value in limited-stage cHL (P = 0.048). PD-1 is an independent prognostic factor in cHL and may allow the identification of a subgroup of patients with limited-stage cHL who require more intensive therapy and who may benefit from anti-PD-1 agents. PMID:26678894

  2. Mechanisms of Indirect Acute Lung Injury: A Novel Role for the Co-Inhibitory Receptor, Programmed Death-1 (PD-1)

    PubMed Central

    Monaghan, Sean F.; Thakkar, Rajan K.; Heffernan, Daithi S.; Huang, Xin; Chung, Chun-Shiang; Lomas-Neira, Joanne; Cioffi, William G.; Ayala, Alfred

    2011-01-01

    Objective To determine the contribution of PD-1 in the morbidity and mortality associated with the development of indirect-acute lung injury Summary Background Data The immune cell interaction(s) leading to indirect-acute lung injury are not completely understood. In this respect, while we have recently shown that the murine cell surface co-inhibitory receptor, Programmed Cell death receptor (PD)-1, has a role in septic morbidity/mortality that is mediated in part through the effects on the innate immune arm. However, it is not know if PD-1 has a role in the development of indirect-acute lung injury and how this may be mediated at a cellular level. Methods PD-1 −/− mice were used in a murine model of indirect-acute lung injury (hemorrhagic shock followed 24 h after with cecal ligation & puncture-septic challenge) and compared to wild type controls. Groups were initially compared for survival and subsequently for markers of pulmonary inflammation, influx of lymphocytes and neutrophils, and expression of PD-1 and its ligand, PD-L1. In addition, peripheral blood leukocytes of patients with indirect-acute lung injury were examined to assess changes in cellular PD-1 expression relative to mortality. Results PD-1 −/− mice showed improved survival compared to wild type controls. In the mouse lung, CD4+, CD11c+ and Gr-1+ cells showed increased PD-1 expression in response to indirect-acute lung injury. However, while the rise in BAL fluid protein concentrations, lung IL-6, and lung MCP-1 were similar between PD-1 −/− and wild type animals subjected to indirect acute lung injury, the PD-1 −/− animals that were subjected to shock/septic challenge had reduced CD4:CD8 ratios, TNF-α levels, MPO activity, and caspase 3 levels in the lung. Comparatively, we observed that humans, who survived their acute lung injury, had significantly lower expression of PD-1 on T cells. Conclusions PD-1 expression contributes to mortality following the induction of indirect

  3. The Expression of Programmed Death-1 in Circulating CD4+ and CD8+ T Cells during Hepatitis B Virus Infection Progression and Its Correlation with Clinical Baseline Characteristics

    PubMed Central

    Xu, Ping; Chen, Yong-Jing; Chen, Hui; Zhu, Xiao-Yan; Song, Hua-Feng; Cao, Li-Juan

    2014-01-01

    Background/Aims Programmed death-1 (PD-1) expression was investigated in CD4+ and CD8+ T cells from hepatitis B virus (HBV)-infected patients at the chronic hepatitis B (CHB) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) stages. Methods PD-1 expression in circulating CD4+ and CD8+ T cells was detected by flow cytometry. The correlations between PD-1 expression and HBV viral load, alanine aminotransaminase (ALT) levels and aspartate aminotransferase (AST) levels were analyzed using GraphPad Prism 5.0. Results PD-1 expression in CD4+ and CD8+ T cells was significantly increased in both the CHB group and advanced-stage group (LC plus HCC). In the CHB group, PD-1 expression in both CD4+ and CD8+ T cells was positively correlated with the HBV viral load, ALT, and AST levels. However, in the LC plus HCC group, significant correlations between PD-1 expression and the clinical parameters were nearly absent. Conclusions PD-1 expression in peripheral CD4+ and CD8+ T cells is dynamic, changes with HBV infection progression, and is related to HBV viral load and liver function, especially in CHB. PD-1 expression could be utilized as a potential clinical indicator to determine the extent of virus replication and liver injury. PMID:24672661

  4. Effects of interferon-α-transduced tumor cell vaccines and blockade of programmed cell death-1 on the growth of established tumors.

    PubMed

    Omori, R; Eguchi, J; Hiroishi, K; Ishii, S; Hiraide, A; Sakaki, M; Doi, H; Kajiwara, A; Ito, T; Kogo, M; Imawari, M

    2012-09-01

    Interferon-alpha (IFN-α) has strong antitumor effects, and IFN-α gene therapy has been used clinically against some cancers. In this study, we evaluated the efficacy of the combination of IFN-α-transduced tumor cell vaccines and programmed cell death 1 (PD-1) blockade, and investigated the mechanisms of the antitumor effects of the combined therapy. A poorly immunogenic murine colorectal cancer cell line, MC38, was transduced to overexpress IFN-α. In a therapeutic model, parental tumor-bearing mice were inoculated with MC38-IFNα cells and an anti-PD-1 antagonistic antibody. Analyses of immunohistochemistry and tumor-specific lysis were performed. The outgrowth of the established tumors was significantly reduced in mice treated with the combination of IFN-α and anti-PD-1. Immunohistochemical analyses of the therapeutic model showed marked infiltration of CD4(+) cells and CD8(+) cells in the established MC38 tumors of mice treated with both IFN-α and anti-PD-1. Significant tumor-specific cytolysis was detected when splenocytes of mice that were treated with both IFN-α and anti-PD-1 were used as effector cells. These results suggest that blockade of the PD-1 PD-ligand enhanced the Th1-type antitumor immune responses induced by IFN-α. The combination of IFN-α gene-transduced tumor cell vaccines and PD-1 blockade may be a possible candidate for a cancer vaccine for clinical trials. PMID:22790963

  5. Bullous pemphigoid, an autoantibody-mediated disease, is a novel immune-related adverse event in patients treated with anti-programmed cell death 1 antibodies.

    PubMed

    Hwang, Shelley J E; Carlos, Giuliana; Chou, Shaun; Wakade, Deepal; Carlino, Matteo S; Fernandez-Penas, Pablo

    2016-08-01

    Anti-programmed cell death 1 (anti-PD1) antibodies such as pembrolizumab have shown improved progression-free and overall survival in patients with advanced melanoma. Of 124 patients reviewed in Westmead Hospital from May 2012 to November 2015, treated with pembrolizumab for advanced melanoma, we encountered three cases of bullous pemphigoid (BP). We have previously reported a case of BP. In two recent cases, BP was diagnosed early and treated promptly with potent topical or oral steroid. Patients on anti-PD1 antibodies are at a higher risk of developing cutaneous immune-related adverse events such as lichenoid reactions, eczema and vitiligo. No cases of BP were encountered in the previously published cohort of 260 melanoma patients treated with BRAF inhibitors; as such, it appears that BP is associated with anti-PD1 treatment rather than metastatic melanoma. BP appears to be another immune-related adverse event, and clinicians should have a low threshold for performing cutaneous biopsies and immunofluorescence studies in patients on anti-PD1 therapies. PMID:27031539

  6. [Increased expressions of programmed death 1 (PD-1) and its ligands in peripheral CD3(+) T cells and CD19(+) B cells in patients with hepatocellular carcinoma].

    PubMed

    Liu, Wei; Chai, Lin; Liang, Junli; Lu, Zhizhong; Yang, Siwei

    2016-09-01

    Objective To investigate the changes of programmed death 1 (PD-1) and ligands, as well as interferon-γ (IFN-γ) in peripheral blood mononuclear cells (PBMCs) of patients with hepatocellular carcinoma (HCC). Methods The peripheral blood was collected from 15 early HCC patients, 13 progressive HCC patients and 12 healthy volunteers. PBMCs was isolated from the peripheral blood. The expressions of PD-1, PD-L1 and PD-L2 in PBMCs were detected by flow cytometry; the serum level of IFN-γ was determined by ELISA; the correlation of PD-1 and IFN-γ was analyzed with Pearson's correlation and One-way ANOVA. Results The expression levels of PD-1, PD-L1 and PD-L2 in CD3(+) T cells and CD19(+) B cells and serum IFN-γ level in progressive HCC patients were significantly higher than those in the healthy group and early HCC patients. The expression levels of PD-1, PD-L1 and PD-L2 in the CD3(+) T cells and CD19(+) B cells of the HCC patients were positively correlated with IFN-γ. Conclusion The expression levels of PD-1, PD-L1 and PD-L2 increase in the PBMCs of HCC patients; PD-1 and PD-L1 are correlated with IFN-γ level. PMID:27609582

  7. Programmed Death-1 Ligand 2-Mediated Regulation of the PD-L1 to PD-1 Axis Is Essential for Establishing CD4(+) T Cell Immunity.

    PubMed

    Karunarathne, Deshapriya S; Horne-Debets, Joshua M; Huang, Johnny X; Faleiro, Rebecca; Leow, Chiuan Yee; Amante, Fiona; Watkins, Thomas S; Miles, John J; Dwyer, Patrick J; Stacey, Katryn J; Yarski, Michael; Poh, Chek Meng; Lee, Jason S; Cooper, Matthew A; Rénia, Laurent; Richard, Derek; McCarthy, James S; Sharpe, Arlene H; Wykes, Michelle N

    2016-08-16

    Many pathogens, including Plasmodium spp., exploit the interaction of programmed death-1 (PD-1) with PD-1-ligand-1 (PD-L1) to "deactivate" T cell functions, but the role of PD-L2 remains unclear. We studied malarial infections to understand the contribution of PD-L2 to immunity. Here we have shown that higher PD-L2 expression on blood dendritic cells, from Plasmodium falciparum-infected individuals, correlated with lower parasitemia. Mechanistic studies in mice showed that PD-L2 was indispensable for establishing effective CD4(+) T cell immunity against malaria, because it not only inhibited PD-L1 to PD-1 activity but also increased CD3 and inducible co-stimulator (ICOS) expression on T cells. Importantly, administration of soluble multimeric PD-L2 to mice with lethal malaria was sufficient to dramatically improve immunity and survival. These studies show immuno-regulation by PD-L2, which has the potential to be translated into an effective treatment for malaria and other diseases where T cell immunity is ineffective or short-lived due to PD-1-mediated signaling. PMID:27533014

  8. Mice lacking Programmed cell death-1 show a role for CD8(+) T cells in long-term immunity against blood-stage malaria.

    PubMed

    Horne-Debets, Joshua M; Karunarathne, Deshapriya S; Faleiro, Rebecca J; Poh, Chek Meng; Renia, Laurent; Wykes, Michelle N

    2016-01-01

    Even after years of experiencing malaria, caused by infection with Plasmodium species, individuals still have incomplete immunity and develop low-density parasitemia on re-infection. Previous studies using the P. chabaudi (Pch) mouse model to understand the reason for chronic malaria, found that mice with a deletion of programmed cell death-1 (PD-1KO) generate sterile immunity unlike wild type (WT) mice. Here we investigated if the mechanism underlying this defect during acute immunity also impacts on long-term immunity. We infected WT and PD-1KO mice with Pch-malaria and measured protection as well as immune responses against re-infections, 15 or 20 weeks after the original infection had cleared. WT mice showed approximately 1% parasitemia compared to sterile immunity in PD-1KO mice on re-infection. An examination of the mechanisms of immunity behind this long-term protection in PD-1KO mice showed a key role for parasite-specific CD8(+) T cells even when CD4(+) T cells and B cells responded to re-infection. These studies indicate that long-term CD8(+) T cell-meditated protection requires consideration for future malaria vaccine design, as part of a multi-cell type response. PMID:27217330

  9. Mice lacking Programmed cell death-1 show a role for CD8+ T cells in long-term immunity against blood-stage malaria

    PubMed Central

    Horne-Debets, Joshua M.; Karunarathne, Deshapriya S.; Faleiro, Rebecca J.; Poh, Chek Meng; Renia, Laurent; Wykes, Michelle N.

    2016-01-01

    Even after years of experiencing malaria, caused by infection with Plasmodium species, individuals still have incomplete immunity and develop low-density parasitemia on re-infection. Previous studies using the P. chabaudi (Pch) mouse model to understand the reason for chronic malaria, found that mice with a deletion of programmed cell death-1 (PD-1KO) generate sterile immunity unlike wild type (WT) mice. Here we investigated if the mechanism underlying this defect during acute immunity also impacts on long-term immunity. We infected WT and PD-1KO mice with Pch-malaria and measured protection as well as immune responses against re-infections, 15 or 20 weeks after the original infection had cleared. WT mice showed approximately 1% parasitemia compared to sterile immunity in PD-1KO mice on re-infection. An examination of the mechanisms of immunity behind this long-term protection in PD-1KO mice showed a key role for parasite-specific CD8+ T cells even when CD4+ T cells and B cells responded to re-infection. These studies indicate that long-term CD8+ T cell-meditated protection requires consideration for future malaria vaccine design, as part of a multi-cell type response. PMID:27217330

  10. Mathematics and Molecules: Exploring Connections via Programming.

    ERIC Educational Resources Information Center

    Ploger, Don; Carlock, Margaret

    1996-01-01

    Examines the self-directed activity of two students who learned about molecular structure by writing computer programs. The programs displayed the solution of a mathematics problem, then the programs were extended to represent several classes of organic molecules. Different ways to enhance mathematical connections to chemistry education are…

  11. The Expression of Programmed Death-1 on CD4+ and CD8+ T Lymphocytes in Patients with Type 2 Diabetes and Severe Sepsis

    PubMed Central

    Li, Chunsheng; Shao, Rui

    2016-01-01

    Objective To investigate the expression of Programmed death-1 (PD-1) on T lymphocytes in patients with type 2 diabetes mellitus (T2DM) and severe sepsis, we determined PD-1 expression on CD4+ and CD8+ T lymphocytes of patients with T2DM, severe sepsis, and T2DM combined with severe sepsis. Research Design and Methods This prospective and observational study included 50 healthy controls, 80 cases of T2DM without infection (T2DM group), 88 cases of severe sepsis without T2DM (SS group), and 77 cases of severe sepsis combined with T2DM (SS+T2DM group). Expression of peripheral blood PD-1+ CD4+ T cells and PD-1+ CD8+ T cells were compared between these 4 groups. Then, 28-day survival of the SS and SS+T2DM patients was assessed, and the expression of PD-1 on T cells was also compared between survivors and non-survivors. Results Percentages of PD-1+ CD4+ T cells and PD-1+ CD8+ T cells were higher in the T2DM group than in the healthy control group, and were highest in the SS and SS+T2DM groups. However, the expression of PD-1 on T cells and the mortality showed no significant difference between the SS and SS+T2DM groups. The expression of PD-1 on T cells was higher in non-survivors than survivors, but within the survivor group or non-survivor group, no difference can be detected between those with T2DM and those without T2DM. Conclusion The expression of PD-1 on T cells was increased in both T2DM and severe septic patients, but combining T2DM did not cause a further increase on the PD-1 expression in patients with severe sepsis. PMID:27459386

  12. Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope specificity, T-cell receptor clonotype usage and antigen load

    PubMed Central

    Kløverpris, Henrik N.; McGregor, Reuben; McLaren, James E.; Ladell, Kristin; Stryhn, Anette; Koofhethile, Catherine; Brener, Jacqui; Chen, Fabian; Riddell, Lynn; Graziano, Luzzi; Klenerman, Paul; Leslie, Alasdair; Buus, Søren; Price, David A.; Goulder, Philip

    2014-01-01

    Objectives: Although CD8+ T cells play a critical role in the control of HIV-1 infection, their antiviral efficacy can be limited by antigenic variation and immune exhaustion. The latter phenomenon is characterized by the upregulation of multiple inhibitory receptors, such as programmed death-1 (PD-1), CD244 and lymphocyte activation gene-3 (LAG-3), which modulate the functional capabilities of CD8+ T cells. Design and methods: Here, we used an array of different human leukocyte antigen (HLA)-B∗15 : 03 and HLA-B∗42 : 01 tetramers to characterize inhibitory receptor expression as a function of differentiation on HIV-1-specific CD8+ T-cell populations (n = 128) spanning 11 different epitope targets. Results: Expression levels of PD-1, but not CD244 or LAG-3, varied substantially across epitope specificities both within and between individuals. Differential expression of PD-1 on T-cell receptor (TCR) clonotypes within individual HIV-1-specific CD8+ T-cell populations was also apparent, independent of clonal dominance hierarchies. Positive correlations were detected between PD-1 expression and plasma viral load, which were reinforced by stratification for epitope sequence stability and dictated by effector memory CD8+ T cells. Conclusion: Collectively, these data suggest that PD-1 expression on HIV-1-specific CD8+ T cells tracks antigen load at the level of epitope specificity and TCR clonotype usage. These findings are important because they provide evidence that PD-1 expression levels are influenced by peptide/HLA class I antigen exposure. PMID:24906112

  13. Expression of Programmed Cell Death 1 Ligands (PD-L1 and PD-L2) in Histiocytic and Dendritic Cell Disorders.

    PubMed

    Xu, Jie; Sun, Heather H; Fletcher, Christopher D M; Hornick, Jason L; Morgan, Elizabeth A; Freeman, Gordon J; Hodi, F Stephen; Pinkus, Geraldine S; Rodig, Scott J

    2016-04-01

    Programmed cell death 1 ligands 1 and 2 (PD-L1 and PD-L2) are cell surface proteins expressed by activated antigen-presenting cells and by select malignancies that bind PD-1 on T cells to inhibit immune responses. Antibodies targeting PD-1 or PD-L1 elicit antitumor immunity in a subset of patients, and clinical response correlates with PD-1 ligand expression by malignant or immune cells within the tumor microenvironment. We examined the expression of PD-1 ligands on subsets of antigen-presenting cells and 87 histiocytic and dendritic cell disorders including those that are benign, borderline, and malignant. Within reactive lymphoid tissue, strong PD-L1 is detected on most macrophages, subsets of interdigitating dendritic cells, and plasmacytoid dendritic cells, but not on follicular dendritic cells or Langerhans cells. Macrophage/dendritic cell subsets do not express discernible PD-L2. Seven of 7 cases of sarcoidosis (100%), 6 of 6 cases of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) (100%), 2 of 11 cases of Rosai-Dorfman disease (18%), and 3 of 15 cases of Langerhans cell histiocytosis (20%) exhibited positivity for PD-L1. All cases of sarcoidosis were also positive for PD-L2. Seven of 14 histiocytic sarcomas (50%), 2 of 5 interdigitating dendritic cell sarcomas (40%), 10 of 20 follicular dendritic cell sarcomas (50%), and none of 9 blastic plasmacytoid dendritic cell neoplasms were positive for PD-L1. Eleven of 20 (55%) follicular dendritic cell sarcomas were also positive for PD-L2. PD-L1 and PD-L2 are useful new markers for identifying select histiocyte and dendritic cell disorders and reveal novel patient populations as rational candidates for immunotherapy. PMID:26752545

  14. Programmed death 1 regulates memory phenotype CD4 T cell accumulation, inhibits expansion of the effector memory phenotype subset and modulates production of effector cytokines.

    PubMed

    Charlton, Joanna J; Tsoukatou, Debbie; Mamalaki, Clio; Chatzidakis, Ioannis

    2015-01-01

    Memory phenotype CD4 T cells are found in normal mice and arise through response to environmental antigens or homeostatic mechanisms. The factors that regulate the homeostasis of memory phenotype CD4 cells are not clear. In the present study we demonstrate that there is a marked accumulation of memory phenotype CD4 cells, specifically of the effector memory (T(EM)) phenotype, in lymphoid organs and tissues of mice deficient for the negative co-stimulatory receptor programmed death 1 (PD-1). This can be correlated with decreased apoptosis but not with enhanced homeostatic turnover potential of these cells. PD-1 ablation increased the frequency of memory phenotype CD4 IFN-γ producers but decreased the respective frequency of IL-17A-producing cells. In particular, IFN-γ producers were more abundant but IL-17A producing cells were more scarce among PD-1 KO T(EM)-phenotype cells relative to WT. Transfer of peripheral naïve CD4 T cells suggested that accumulated PD-1 KO T(EM)-phenotype cells are of peripheral and not of thymic origin. This accumulation effect was mediated by CD4 cell-intrinsic mechanisms as shown by mixed bone marrow chimera experiments. Naïve PD-1 KO CD4 T cells gave rise to higher numbers of TEM-phenotype lymphopenia-induced proliferation memory cells. In conclusion, we provide evidence that PD-1 has an important role in determining the composition and functional aspects of memory phenotype CD4 T cell pool. PMID:25803808

  15. Interacting Alleles of the Coinhibitory Immunoreceptor Genes Cytotoxic T-Lymphocyte Antigen 4 and Programmed Cell-Death 1 Influence Risk and Features of Primary Biliary Cirrhosis

    PubMed Central

    Juran, Brian D.; Atkinson, Elizabeth J.; Schlicht, Erik M.; Fridley, Brooke L.; Petersen, Gloria M.; Lazaridis, Konstantinos N.

    2012-01-01

    Autoimmune diseases such as primary biliary cirrhosis (PBC) result from failure in the immune mechanisms that establish and maintain self-tolerance. Evidence suggests that these processes are shared among the spectrum of autoimmune syndromes and are likely genetically determined. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell-death 1 (PDCD1) are two genes encoding coinhibitory immunoreceptors that harbor polymorphisms with demonstrated associations to multiple autoimmune disorders. We aimed to assess functional single nucleotide polymorphisms (SNPs) in these two genes for association with PBC. SNPs in CTLA4 and PDCD1 were genotyped in 351 PBC patients and 205 controls. Allele and genotype frequencies were evaluated for association with PBC and/or antimitochondrial antibody (AMA) positivity with logistic regression. Haplotypes were inferred with an expectation-maximization algorithm, and allelic interaction was analyzed by logistic regression modeling. Individual SNPs demonstrated no association to PBC. However, the GG genotype of CTLA4 49AG was significantly associated with AMA positivity among the PBC patients. Also, individual SNPs and a haplotype of CTLA4 as well as a rare genotype of the PDCD1 SNP PD1.3 were associated with orthotopic liver transplantation. As well, we identified the influence of an interaction between the putatively autoimmune-protective CTLA4 49AG:CT60 AA haplotype and autoimmune-risk PDCD1 PD1.3 A allele on development of PBC. Conclusion Our findings illustrate the complex nature of the genetically induced risk of PBC and emphasize the importance of considering definable subphenotypes of disease, such as AMA positivity, or definitive measures of disease severity/progression, like orthotopic liver transplantation, when genetic analyses are being performed. Comprehensive screening of genes involved with immune function will lead to a greater understanding of the genetic component of autoimmunity in PBC while furthering our

  16. Do programmed death 1 (PD-1) and its ligand (PD-L1) play a role in patients with non-clear cell renal cell carcinoma?

    PubMed

    Abbas, Mahmoud; Steffens, Sandra; Bellut, Maria; Becker, Jan U; Großhennig, Anika; Eggers, Hendrik; Wegener, Gerd; Kuczyk, Markus A; Kreipe, Hans H; Grünwald, Viktor; Schrader, Andres J; Ivanyi, Philipp

    2016-06-01

    Clinical trials targeting programmed death 1 (PD-1) and its ligand PD-L1 (PD-L1) for metastatic renal cell cancer (RCC) are ongoing. The aim of this study is to validate their roles as prognostic markers in non-clear cell (non-cc) RCC. Sixty-four non-cc RCC tissue specimens were collected from patients undergoing renal tumor surgery. Expressions of biomarkers were assessed using immunohistochemistry and compared with clinical characteristics. Survival analyses were performed with a median follow-up of 77.5 (range: 0-176) months. No significant correlations were found for PD-1(+) tumor-infiltrating mononuclear cells (TIMC) or PD-L1(+) expression and clinical attributes in patients with non-cc RCC. Kaplan-Meier analysis revealed no differences in 5- and 10-year cancer-specific survival (CSS) for PD-1(-) TIMC compared to PD-1(+) TIMC (71.4 and 63 % versus 72.2 and 61.9 %; p = 0.88). Intratumoral expression of PD-L1 did not appear to influence the 5- and 10-year CSS significantly, even though a trend was identified (68 and 53.6 % versus 80.1 and 75.7 %; p = 0.08). In multivariate analysis, neither PD-1(+) TIMC nor intratumoral PD-L1(+) expression proved to be independent predictors of CSS (p = 0.99 and p = 0.68, respectively). Our study demonstrates that PD-1(+) TIMC and intratumoral PD-L1(+) expression did not significantly impact tumor aggressiveness or clinical outcome in non-ccRCC specimens. Due to rare incidence of non-cc RCC in particular according to PD-L1 expression, further analyzes are warranted. PMID:27165272

  17. Coordination programming of photofunctional molecules.

    PubMed

    Sakamoto, Ryota; Kusaka, Shinpei; Hayashi, Mikihiro; Nishikawa, Michihiro; Nishihara, Hiroshi

    2013-01-01

    Our recent achievements relating to photofunctional molecules are addressed. Section 1 discloses a new concept of photoisomerization. Pyridylpyrimidine-copper complexes undergo a ring inversion that can be modulated by the redox state of the copper center. In combination with an intermolecular photoelectron transfer (PET) initiated by the metal-to-ligand charge transfer (MLCT) transition of the Cu(I) state, we realize photonic regulation of the ring inversion. Section 2 reports on the first examples of heteroleptic bis(dipyrrinato)zinc(II) complexes. Conventional homoleptic bis(dipyrrinato)zinc(II) complexes suffered from low fluorescence quantum yields, whereas the heteroleptic ones feature bright fluorescence even in polar solvents. Section 3 describes our new findings on Pechmann dye, which was first synthesized in 1882. New synthetic procedures for Pechmann dye using dimethyl bis(arylethynyl)fumarate as a starting material gives rise to its new structural isomer. We also demonstrate potentiality of a donor-acceptor-donor type of Pechmann dye in organic electronics. PMID:23563859

  18. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma

    PubMed Central

    Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna

    2016-01-01

    Aims Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. Methods PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset. Results PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively). Conclusions Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity. PMID:26625204

  19. Expression of programmed death-1 ligand (PD-L1) in tumor-infiltrating lymphocytes is associated with favorable spinal chordoma prognosis

    PubMed Central

    Zou, Ming-Xiang; Peng, An-Bo; Lv, Guo-Hua; Wang, Xiao-Bin; Li, Jing; She, Xiao-Ling; Jiang, Yi

    2016-01-01

    Aberrant expression of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) proteins alters human immunoresponse and promotes tumor development and progression. We assessed the expression status of PD-1 and PD-L1 in spinal chordoma tissue specimens and their association with clinicopathological characteristics of patients. Formalin-fixed paraffin-embedded tumor samples from 54 patients with spinal chordoma were collected for immunohistochemical analysis of PD-1 and PD-L1 expression. The association of the expression levels of PD-1 and PD-L1 with clinicopathological variables and survival data were statistically analyzed. Lymphocyte infiltrates were present in all 54 patient samples. Of 54 samples, 37 (68.5%) had both positive PD-1 and PD-L1 expression in tumor cell membrane. Moreover, 38 (70.4%) and 12 (22.2%) had positive PD-1 and PD-L1 expression in tumor-infiltrating lymphocytes (TILs), respectively. Tumors with positive PD-L1 expression were significantly associated with advanced stages of chordoma (p = 0.041) and TIL infiltration (p = 0.005), and had a borderline association with tumor grade (p = 0.051). However, positive tumor PD-L1 expression was not significantly associated with local recurrence-free survival (LRFS) or overall survival (OS). PD-1 expression in TILs was associated with poor LRFS (χ2 = 10.051, p = 0.002, log-rank test). Multivariate analysis showed that PD-L1 expression only in TILs was an independent predictor for LRFS (HR = 0.298, 95% CI: 0.098-0.907, p = 0.033), and OS (HR = 0.188, 95% CI: 0.051-0.687, p = 0.011) in spinal chordoma patients. In conclusion, PD-L1 expression in TILs was an independent predictor for both LRFS and OS in spinal chordoma patients. Our findings suggest that the PD-1/PD-L1 pathway may be a novel therapeutic target for the immunotherapy of chordoma. PMID:27508049

  20. Role of soluble programmed death-1 (sPD-1) and sPD-ligand 1 in patients with cystic echinococcosis

    PubMed Central

    LI, YANHUA; XIAO, YUNFENG; SU, MINGQUAN; ZHANG, RONG; DING, JIANBING; HAO, XIAOKE; MA, YUEYUN

    2016-01-01

    The programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) signaling pathway is a negative regulatory mechanism that inhibits T cell proliferation and cytokine production. Soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1), are also involved in regulation of the PD-1/PD-L1 signaling pathway. In the present study, the expression levels of sPD-1 and sPD-L1, as well as those of T helper (Th)1 [including interleukin (IL)-2 and interferon gamma], Th2 (including IL-4, IL-6 and IL-10) and Th17 (including interleukin 17) cell cytokines, were measured in the sera of patients with cystic echinococcosis (CE). Measurements were performed prior to and following after surgery and treatment with cyclic albendazole to investigate the effects of sPD-1 and sPD-L1 in patients with CE. Cytokine expression levels were measured using cytokine bead array and the expression levels of sPD-1 and sPD-L1 were measured using ELISA. In addition, in vitro stimulation was used to detect whether sPD-L1 has a negative regulatory effect on cytokine secretion or homeostasis. The present study observed significantly higher levels of sPD-L1 in patients with CE compared with healthy controls. Significantly elevated levels of Th2 cytokines in the sera of patients with CE were also observed. The results also suggest that there is an imbalanced expression of Th1 and Th2 cells during CE. In addition, it was demonstrated that sPD-1 and sPD-L1 are regulatory factors to the PD-1/PD-L1 signaling pathway, each having opposite effect, suggesting that they regulate the immune response to CE infection by creating a dynamic balance. In conclusion, sPD-L1 may play an important role in maintaining homeostasis in hosts with CE. PMID:26889250

  1. Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo

    PubMed Central

    Yasuda, S; Sho, M; Yamato, I; Yoshiji, H; Wakatsuki, K; Nishiwada, S; Yagita, H; Nakajima, Y

    2013-01-01

    Recent basic and clinical studies have shown that the programmed death ligand (PD-L)/PD-1 pathway has a significant role in tumour immunity, and its blockade has a therapeutic potential against several human cancers. We hypothesized that anti-angiogeneic treatment might augment the efficacy of PD-1 blockade. To this end, we evaluated combining the blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2) in a murine cancer model using Colon-26 adenocarcinoma. Interestingly, simultaneous treatment with anti-PD-1 and anti-VEGFR2 monoclonal antibodies (mAbs) inhibited tumour growth synergistically in vivo without overt toxicity. Blocking VEGFR2 inhibited tumour neovascularization significantly, as demonstrated by the reduced number of microvessels, while PD-1 blockade had no impact on tumour angiogenesis. PD-1 blockade might promote T cell infiltration into tumours and significantly enhanced local immune activation, as shown by the up-regulation of several proinflammatory cytokine expressions. Importantly, VEGFR2 blockade did not interfere with T cell infiltration and immunological activation induced by PD-1 blockade. In conclusion, simultaneous blockade of PD-1 and VEGFR2 induced a synergistic in-vivo anti-tumour effect, possibly through different mechanisms that might not be mutually exclusive. This unique therapeutic strategy may hold significant promise for future clinical application. PMID:23600839

  2. Concomitant targeting of programmed death-1 (PD-1) and CD137 improves the efficacy of radiotherapy in a mouse model of human BRAFV600-mutant melanoma.

    PubMed

    Kroon, Paula; Gadiot, Jules; Peeters, Marlies; Gasparini, Alessia; Deken, Marcel A; Yagita, Hideo; Verheij, Marcel; Borst, Jannie; Blank, Christian U; Verbrugge, Inge

    2016-06-01

    T cell checkpoint blockade with antibodies targeting programmed cell death (ligand)-1 (PD-1/PD-L1) and/or cytotoxic T lymphocyte-antigen 4 (CTLA-4) has improved therapy outcome in melanoma patients. However, a considerable proportion of patients does not benefit even from combined α-CTLA-4 and α-PD-1 therapy. We therefore examined to which extent T cell (co)stimulation and/or stereotactic body radiation therapy (SBRT) could further enhance the therapeutic efficacy of T cell checkpoint blockade in a genetically engineered mouse melanoma model that is driven by PTEN-deficiency, and BRAFV600 mutation, as in human, but lacks the sporadic UV-induced mutations. Tumor-bearing mice were treated with different combinations of immunomodulatory antibodies (α-CTLA-4, α-PD-1, α-CD137) or interleukin-2 (IL-2) alone or in combination with SBRT. None of our immunotherapeutic approaches (alone or in combination) had any anti-tumor efficacy, while SBRT alone delayed melanoma outgrowth. However, α-CD137 combined with α-PD-1 antibodies significantly enhanced the anti-tumor effect of SBRT, while the anti-tumor effect of SBRT was not enhanced by interleukin-2, or the combination of α-CTLA-4 and α-PD-1. We conclude that α-CD137 and α-PD-1 antibodies were most effective in enhancing SBRT-induced tumor growth delay in this mouse melanoma model, outperforming the ability of IL-2, or the combination of α-CTLA-4 and α-PD-1 to synergize with SBRT. Given the high mutational load and increased immunogenicity of human melanoma with the same genotype, our findings encourage testing α-CD137 and α-PD-1 alone or in combination with SBRT clinically, particularly in patients refractory to α-CTLA-4 and/or α-PD-1 therapy. PMID:27160390

  3. Disabling Immune Tolerance by Programmed Death-1 Blockade With Pidilizumab After Autologous Hematopoietic Stem-Cell Transplantation for Diffuse Large B-Cell Lymphoma: Results of an International Phase II Trial

    PubMed Central

    Armand, Philippe; Nagler, Arnon; Weller, Edie A.; Devine, Steven M.; Avigan, David E.; Chen, Yi-Bin; Kaminski, Mark S.; Holland, H. Kent; Winter, Jane N.; Mason, James R.; Fay, Joseph W.; Rizzieri, David A.; Hosing, Chitra M.; Ball, Edward D.; Uberti, Joseph P.; Lazarus, Hillard M.; Mapara, Markus Y.; Gregory, Stephanie A.; Timmerman, John M.; Andorsky, David; Or, Reuven; Waller, Edmund K.; Rotem-Yehudar, Rinat; Gordon, Leo I.

    2013-01-01

    Purpose The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade. Patients and Methods We conducted an international phase II study of pidilizumab, an anti–PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT. Results Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E–bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab. Conclusion This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease. PMID:24127452

  4. Expression of Programmed Cell Death 1 Ligand 2 (PD-L2) is a Distinguishing Feature of Primary Mediastinal (Thymic) Large B-cell Lymphoma and Associated with PDCD1LG2 Copy Gain

    PubMed Central

    Shi, Min; Roemer, Margaretha GM; Chapuy, Bjoern; Liao, Xiaoyun; Sun, Heather; Pinkus, Geraldine S.; Shipp, Margaret A.; Freeman, Gordon J.; Rodig, Scott J.

    2016-01-01

    Primary mediastinal (thymic) large B-cell lymphoma (PMBL) and diffuse large B-cell lymphoma (DLBCL) are tumors with distinct clinical and molecular characteristics that are difficult to distinguish by histopathological and phenotypic analyses alone. Programmed cell death 1 ligand 2 (PD-L2) is a cell surface protein expressed by activated macrophages and dendritic cells that binds PD-1 on T-cells to inhibit immune responses. Amplification and/or translocations involving chromosome 9p24.1, a region that includes PDCD1LG2 encoding PD-L2, is a common event in PMBL but not DLBCL and suggests that PD-L2 expression might be a distinguishing feature of PMBL. We developed an assay for the immunohistochemical detection of PD-L2 protein in fixed biopsy specimens (PD-L2 IHC) which we applied to a cohort of PMBLs and DLBCLs. For a subset of cases, we correlated the results of PD-L2 IHC with PDCD1LG2 copy number as determined by qPCR. Twenty-three of 32 (72%) PMBLs but only 1 of 37 (3%) DLBCLs were positive by PD-L2 IHC. Among PMBLs with PDCD1LG2 copy number gain, all were positive by PD-L2 IHC. One PMBL without copy number gain was positive by PD-L2 IHC. When expressed in PMBL, PD-L2 was restricted to tumor cells and not detected on intra-tumoral macrophages. We conclude that PD-L2 protein is robustly expressed by the majority of PMBLs but only rare DLBCLs and often associated with PDCD1LG2 copy gain. PD-L2 IHC may serve as a useful ancillary test for distinguishing PMBL from DLBCL and for the rational selection of patients for therapeutic antibodies that inhibit PD-1 signaling. PMID:25025450

  5. Expression of programmed death-1 in primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma, cutaneous pseudo-T-cell lymphoma, and other types of cutaneous T-cell lymphoma.

    PubMed

    Cetinözman, Fatma; Jansen, Patty M; Willemze, Rein

    2012-01-01

    In this study we investigated whether programmed death-1 (PD-1) could serve as a useful diagnostic marker to differentiate between primary cutaneous CD4 small/medium-sized pleomorphic T-cell lymphoma (PCSM-TCL) and cutaneous pseudo-T-cell lymphomas on the one hand and other types of cutaneous T-cell lymphomas (CTCLs) on the other. Formalin-fixed, paraffin-embedded skin biopsies from 26 patients with PCSM-TCL or pseudo-T-cell lymphoma, including 1 patient with a lymphomatoid drug eruption, and 52 skin biopsies from other types of CTCLs were stained for PD-1. In addition, PD-1-positive cases were stained with antibodies against BCL6, CXCL13, and CD10 to determine a possible relationship with follicular helper T (TFH) cells. In all 26 cases of PCSM-TCL or pseudo-T-cell lymphoma, the medium-sized to large-sized atypical T cells consistently expressed PD-1, BCL6, and CXCL13 but not CD10. PD-1 expression was found in only 2 of 21 cases of mycosis fungoides and in only 2 of 16 cases of cutaneous peripheral T-cell lymphoma, unspecified. All 4 patients with an aggressive epidermotropic cytotoxic CD8 CTCL and all 11 cases with a primary cutaneous CD30 lymphoproliferative disorder were negative for PD-1. In conclusion, PD-1 is typically expressed by atypical cells in PCSM-TCL and pseudo-T-cell lymphoma but is not expressed or is rarely expressed in other types of CTCLs. Therefore, it may serve as a suitable adjunct in differential diagnosis. Our results demonstrate that the atypical cells in PCSM-TCL and pseudo-T-cell lymphomas share a common TFH phenotype and support the view that most cases classified nowadays as PCSM-TCL are identical to cutaneous pseudo-T-cell lymphomas described previously. PMID:21989349

  6. Roles of the programmed cell death 1, T cell immunoglobulin mucin-3, and cluster of differentiation 288 pathways in the low reactivity of invariant natural killer T cells after chronic hepatitis B virus infection.

    PubMed

    Yang, Zhixin; Lei, Yu; Chen, Chunbo; Ren, Hong; Shi, Tongdong

    2015-10-01

    One of the main responses of invariant natural killer T (iNKT) cells to antigen stimulation is the rapid production of interleukin (IL)-4 and interferon (IFN)-γ cytokines. There is a decline in the function of iNKT cells in chronic hepatitis B (CHB) patients. In this study, we explored the impact of programmed cell death 1 (PD-1), T cell immunoglobulin mucin-3 (Tim-3), and cluster of differentiation 28 (CD28) expression on iNKT cell functions in CHB patients. Flow cytometry was used to test iNKT frequencies and levels of PD-1, Tim-3, CD28, IL-4, and IFN-γ secreted by iNKT cells. An enzyme-linked immunosorbent assay (ELISA) was used to measure IL-4 and IFN-γ secretion upon α-galactosylceramide (α-GalCer) activation ex vivo. We found that the levels of expression of PD-1 and Tim-3 from iNKT cells in CHB patients were significantly higher than in healthy donors (p < 0.05), but there was lower expression of CD28 (p < 0.05) and an impaired capability to produce IL-4 and IFN-γ (p < 0.05). In vitro α-GalCer stimulation upregulated the expression of PD-1(+) iNKT cells (p < 0.05), Tim-3(+) iNKT cells (p < 0.05), and CD28(+) iNKT cells (p < 0.05). In response to combination therapies consisting of α-GalCer and anti-PDL1 monoclonal antibody (mAb) and/or anti-Tim-3 mAbs and/or anti-CD80/anti-CD28 mAbs, IL-4(+) and IFN-γ(+) iNKT cells demonstrated different degrees of growth (p < 0.05). The functional decline of iNKT cells was closely related to the decrease in CD28 expression and the increases of Tim-3 and PD-1. In addition, clinical antiviral treatment with lamivudine could partially restore the immune function of iNKT cells in CHB patients. PMID:26215444

  7. A Randomized, Double-Blind, Placebo-Controlled Assessment of BMS-936558, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients with Chronic Hepatitis C Virus Infection

    PubMed Central

    Gardiner, David; Lalezari, Jay; Lawitz, Eric; DiMicco, Michael; Ghalib, Rheem; Reddy, K. Rajender; Chang, Kyong-Mi; Sulkowski, Mark; Marro, Steven O’; Anderson, Jeffrey; He, Bing; Kansra, Vikram; McPhee, Fiona; Wind-Rotolo, Megan; Grasela, Dennis; Selby, Mark; Korman, Alan J.; Lowy, Israel

    2013-01-01

    Expression of the programmed death 1 (PD-1) receptor and its ligands are implicated in the T cell exhaustion phenotype which contributes to the persistence of several chronic viral infections, including human hepatitis C virus (HCV). The antiviral potential of BMS-936558 (MDX-1106) – a fully human anti-PD-1 monoclonal immunoglobulin-G4 that blocks ligand binding – was explored in a proof-of-concept, placebo-controlled single-ascending-dose study in patients (N = 54) with chronic HCV infection. Interferon-alfa treatment-experienced patients (n = 42) were randomized 5∶1 to receive a single infusion of BMS-936558 (0.03, 0.1, 0.3, 1.0, 3.0 mg/kg [n = 5 each] or 10 mg/kg [n = 10]) or of placebo (n = 7). An additional 12 HCV treatment-naïve patients were randomized to receive 10 mg/kg BMS-936558 (n = 10) or placebo (n = 2). Patients were followed for 85 days post-dose. Five patients who received BMS-936558 (0.1 [n = 1] or 10 mg/kg) and one placebo patient achieved the primary study endpoint of a reduction in HCV RNA ≥0.5 log10 IU/mL on at least 2 consecutive visits; 3 (10 mg/kg) achieved a >4 log10 reduction. Two patients (10 mg/kg) achieved HCV RNA below the lower limit of quantitation (25 IU/mL), one of whom (a prior null-responder) remained RNA-undetectable 1 year post-study. Transient reductions in CD4+, CD8+ and CD19+ cells, including both naïve and memory CD4+ and CD8+ subsets, were observed at Day 2 without evidence of immune deficit. No clinically relevant changes in immunoglobulin subsets or treatment-related trends in circulating cytokines were noted. BMS-936558 exhibited dose-related exposure increases, with a half-life of 20–24 days. BMS-936558 was mostly well tolerated. One patient (10 mg/kg) experienced an asymptomatic grade 4 ALT elevation coincident with the onset of a 4-log viral load reduction. Six patients exhibited immune-related adverse events of mild-to-moderate intensity, including two cases of

  8. Programmed necrosis in inflammation: Toward identification of the effector molecules.

    PubMed

    Wallach, David; Kang, Tae-Bong; Dillon, Christopher P; Green, Douglas R

    2016-04-01

    Until recently, programmed cell death was conceived of as a single set of molecular pathways. We now know of several distinct sets of death-inducing mechanisms that lead to differing cell-death processes. In one of them--apoptosis--the dying cell affects others minimally. In contrast, programmed necrotic cell death causes release of immunostimulatory intracellular components after cell-membrane rupture. Defining the in vivo relevance of necrotic death is hampered because the molecules initiating it [such as receptor-interacting protein kinase-1 (RIPK1), RIPK3, or caspase-1] also serve other functions. Proteins that participate in late events in two forms of programmed necrosis [mixed lineage kinase domain-like protein (MLKL) in necroptosis and gasdermin-D in pyroptosis] were recently discovered, bringing us closer to identifying molecules that strictly serve in death mediation, thereby providing probes for better assessing its role in inflammation. PMID:27034377

  9. DUO: A general program for calculating spectra of diatomic molecules

    NASA Astrophysics Data System (ADS)

    Yurchenko, Sergei N.; Lodi, Lorenzo; Tennyson, Jonathan; Stolyarov, Andrey V.

    2016-05-01

    DUO is a general, user-friendly program for computing rotational, rovibrational and rovibronic spectra of diatomic molecules. DUO solves the Schrödinger equation for the motion of the nuclei not only for the simple case of uncoupled, isolated electronic states (typical for the ground state of closed-shell diatomics) but also for the general case of an arbitrary number and type of couplings between electronic states (typical for open-shell diatomics and excited states). Possible couplings include spin-orbit, angular momenta, spin-rotational and spin-spin. Corrections due to non-adiabatic effects can be accounted for by introducing the relevant couplings using so-called Born-Oppenheimer breakdown curves. DUO requires user-specified potential energy curves and, if relevant, dipole moment, coupling and correction curves. From these it computes energy levels, line positions and line intensities. Several analytic forms plus interpolation and extrapolation options are available for representation of the curves. DUO can refine potential energy and coupling curves to best reproduce reference data such as experimental energy levels or line positions. DUO is provided as a Fortran 2003 program and has been tested under a variety of operating systems.

  10. Programmed cell death 1 and Helios distinguish TCR-αβ+ double negative (CD4-CD8-) T cells that derive from self-reactive CD8 T cells1

    PubMed Central

    Rodríguez-Rodríguez, Noé; Apostolidis, Sokratis A.; Penaloza-MacMaster, Pablo; Manuel Martín Villa, José; Barouch, Dan H.; Tsokos, George C.; Crispín, José C.

    2015-01-01

    TCR-αβ+ double negative (DN; CD4-CD8-) T cells represent a poorly understood cellular subset suggested to contribute to the pathogenesis of the autoimmune disease systemic lupus erythematosus. DN T cells have been proposed to derive from CD8+ cells. However, the conditions that govern the loss of CD8 expression after antigen encounter are unknown. Here we tracked the fate of CD8 T cells from transgenic TCR mice exposed to their cognate antigens as self or in the context of infection. We demonstrate that CD8 T cells lose CD8 expression and become DN only when cognate antigen is sensed as self. This process is restricted to tissues where the antigen is present. We also show that DN T cells derived from self-reactive CD8 cells express the inhibitory molecules PD-1 and Helios. These molecules identify a subset of DN T cells in normal mice. A similar population expands when CD8 T cells from repertoires enriched in self-reactive cells (Aire-deficient) are transferred into cognate hosts. Collectively, our data suggest that a subset of DN T cells, identified by the expression of PD-1 and Helios, represent self-reactive cells. Our results provide an explanation for the origin of DN T cells and introduce CD8 loss as a process associated to self-antigen encounter. PMID:25825451

  11. A Computer Program for the Distribution of End-to-End Distances in Polymer Molecules

    ERIC Educational Resources Information Center

    Doorne, William Van; And Others

    1976-01-01

    Describes a Fortran program that illustrates how the end-to-end distances in randomly coiled polymer molecules is affected by varying the number and lengths of chains and the angles between them. (MLH)

  12. Three-Dimensional Chemical Structure Search Using the Conformational Code for Organic Molecules (CCOM) Program.

    PubMed

    Izumi, Hiroshi; Nafie, Laurence A; Dukor, Rina K

    2016-05-01

    Searching the 3D structural fragments of organic molecules is challenging because of structural differences between X-ray and theoretically calculated geometries and the conformational flexibility of substituents. The codification program called Conformational Code for Organic Molecules (CCOM) can be used to unambiguously convert 3D conformational data for various molecules to 1D data. Two deviations from Rule E-5.6 of the International Union of Pure and Applied Chemistry (IUPAC) Rules for Nomenclature of Organic Chemistry were introduced to the CCOM program for 3D fragment searching. First, the search for the highest priority atom was limited to a distance of two bonds from the center bond for dihedral angle determination. Second, for indistinguishable atoms in experimentally observed solution structures, the smallest number of atom index in the molecular model was chosen as the priority atom for dihedral angle determination. A search of the 3D conformational fragment mb_3a6c4c of mevastatin () in combination with the SMiles ARbitrary Target Specification (SMARTS) description suggested that a change in the conformation of this fragment may be the driving force for dissociation of mevastatin from its target protein. Chirality 28:370-375, 2016. © 2016 Wiley Periodicals, Inc. PMID:27040870

  13. Programmed Lab Experiments for Biochemical Investigation of Quorum-Sensing Signal Molecules in Rhizospheric Soil Bacteria.

    PubMed

    Nievas, Fiorela L; Bogino, Pablo C; Giordano, Walter

    2016-05-01

    Biochemistry courses in the Department of Molecular Biology at the National University of Río Cuarto, Argentina, are designed for undergraduate students in biology, microbiology, chemistry, agronomy, and veterinary medicine. Microbiology students typically have previous coursework in general, analytical, and organic chemistry. Programmed sequences of lab experiments allow these students to investigate biochemical problems whose solution is feasible within the context of their knowledge and experience. We previously designed and reported a programmed lab experiment that familiarizes microbiology students with techniques for detection and characterization of quorum-sensing (QS) and quorum-quenching (QQ) signal molecules. Here, we describe a sequence of experiments designed to expand the understanding and capabilities of biochemistry students using techniques for extraction and identification of QS and QQ signal molecules from peanut rhizospheric soil bacteria, including culturing and manipulation of bacteria under sterile conditions. The program provides students with an opportunity to perform useful assays, draw conclusions from their results, and discuss possible extensions of the study. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:256-262, 2016. PMID:27027267

  14. Regulation Effects by Programmed Molecules for Transcription-Based Diagnostic Automata towards Therapeutic Use

    NASA Astrophysics Data System (ADS)

    Hirabayashi, Miki; Ohashi, Hirotada; Kubo, Tai

    We have presented experimental analysis on the controllability of our transcription-based diagnostic biomolecular automata by programmed molecules. Focusing on the noninvasive transcriptome diagnosis by salivary mRNAs, we already proposed the novel concept of diagnostic device using DNA computation. This system consists of the main computational element which has a stem shaped promoter region and a pseudo-loop shaped read-only memory region for transcription regulation through the conformation change caused by the recognition of disease-related biomarkers. We utilize the transcription of malachite green aptamer sequence triggered by the target recognition for observation of detection. This algorithm makes it possible to release RNA-aptamer drugs multiply, different from the digestion-based systems by the restriction enzyme which was proposed previously, for the in-vivo use, however, the controllability of aptamer release is not enough at the previous stage. In this paper, we verified the regulation effect on aptamer transcription by programmed molecules in basic conditions towards the developm! ent of therapeutic automata. These results would bring us one step closer to the realization of new intelligent diagnostic and therapeutic automata based on molecular circuits.

  15. A finite difference Hartree-Fock program for atoms and diatomic molecules

    NASA Astrophysics Data System (ADS)

    Kobus, Jacek

    2013-03-01

    The newest version of the two-dimensional finite difference Hartree-Fock program for atoms and diatomic molecules is presented. This is an updated and extended version of the program published in this journal in 1996. It can be used to obtain reference, Hartree-Fock limit values of total energies and multipole moments for a wide range of diatomic molecules and their ions in order to calibrate existing and develop new basis sets, calculate (hyper)polarizabilities (αzz, βzzz, γzzzz, Az,zz, Bzz,zz) of atoms, homonuclear and heteronuclear diatomic molecules and their ions via the finite field method, perform DFT-type calculations using LDA or B88 exchange functionals and LYP or VWN correlations ones or the self-consistent multiplicative constant method, perform one-particle calculations with (smooth) Coulomb and Krammers-Henneberger potentials and take account of finite nucleus models. The program is easy to install and compile (tarball+configure+make) and can be used to perform calculations within double- or quadruple-precision arithmetic. Catalogue identifier: ADEB_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADEB_v2_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License version 2 No. of lines in distributed program, including test data, etc.: 171196 No. of bytes in distributed program, including test data, etc.: 9481802 Distribution format: tar.gz Programming language: Fortran 77, C. Computer: any 32- or 64-bit platform. Operating system: Unix/Linux. RAM: Case dependent, from few MB to many GB Classification: 16.1. Catalogue identifier of previous version: ADEB_v1_0 Journal reference of previous version: Comput. Phys. Comm. 98(1996)346 Does the new version supersede the previous version?: Yes Nature of problem: The program finds virtually exact solutions of the Hartree-Fock and density functional theory type equations for atoms, diatomic molecules and their ions

  16. SASSIE: A program to study intrinsically disordered biological molecules and macromolecular ensembles using experimental scattering restraints

    NASA Astrophysics Data System (ADS)

    Curtis, Joseph E.; Raghunandan, Sindhu; Nanda, Hirsh; Krueger, Susan

    2012-02-01

    A program to construct ensembles of biomolecular structures that are consistent with experimental scattering data are described. Specifically, we generate an ensemble of biomolecular structures by varying sets of backbone dihedral angles that are then filtered using experimentally determined restraints to rapidly determine structures that have scattering profiles that are consistent with scattering data. We discuss an application of these tools to predict a set of structures for the HIV-1 Gag protein, an intrinsically disordered protein, that are consistent with small-angle neutron scattering experimental data. We have assembled these algorithms into a program called SASSIE for structure generation, visualization, and analysis of intrinsically disordered proteins and other macromolecular ensembles using neutron and X-ray scattering restraints. Program summaryProgram title: SASSIE Catalogue identifier: AEKL_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKL_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License v3 No. of lines in distributed program, including test data, etc.: 3 991 624 No. of bytes in distributed program, including test data, etc.: 826 Distribution format: tar.gz Programming language: Python, C/C++, Fortran Computer: PC/Mac Operating system: 32- and 64-bit Linux (Ubuntu 10.04, Centos 5.6) and Mac OS X (10.6.6) RAM: 1 GB Classification: 3 External routines: Python 2.6.5, numpy 1.4.0, swig 1.3.40, scipy 0.8.0, Gnuplot-py-1.8, Tcl 8.5, Tk 8.5, Mac installation requires aquaterm 1.0 (or X window system) and Xcode 3 development tools. Nature of problem: Open source software to generate structures of disordered biological molecules that subsequently allow for the comparison of computational and experimental results is limiting the use of scattering resources. Solution method: Starting with an all atom model of a protein, for example, users can input

  17. A program for calculating and plotting soft-X-ray optical interaction coefficients for molecules

    NASA Astrophysics Data System (ADS)

    Thomas, M. M.; Davis, J. C.; Jacobsen, C. J.; Perera, R. C. C.

    1990-05-01

    Comprehensive tables for atomic scattering factor components f1 and f2 were compiled by Henke et al. for the extended photon region of 350-10000 eV. Accurate calculations of optical interaction coefficients for absorption, reflection and scattering by material systems (e.g. filters, multi-layers, etc.), which have widespread application, can be based simply upon the atomic scattering factors for the elements comprising the material, except near the absorption threshold energies. These calculations based upon the weighted sum of f1 and f2 for each atomic species present can be very tedious if done by hand. This led us to develop Optical Constants Grapher (OCG), a user-friendly program to perform these calculations on an IBM PC or compatible computer. By entering the chemical formula, density and thickness of up to six molecules, values of f1, f2, mass absorption, transmission efficiencies, attenuation lengths, mirror reflectivities and complex indices of refraction can be calculated and plotted as a function of energy or wavelength. This program and its user's manual are available from the authors.

  18. Avogadro: Free, Open Source, Cross-Platform Computer Program for Building Molecules and Visualizing Structure

    NASA Astrophysics Data System (ADS)

    Hanwell, Marcus; Hutchison, Geoffrey

    2009-03-01

    The Avogadro project is a free, open source approach to building chemical structures. It has integrated analysis, and three-dimensional visualization capabilities. Avogadro also uses external packages to perform quantum structure calculations. The work presented here illustrates a novel approach to working with the results of quantum calculations by visualizing possible molecular orbitals and allowing the user to select orbitals of interest. The Avogadro program allows the user to prepare new jobs for various quantum codes such as GAMESS-US, Q-Chem, Gaussian and Molpro. Due to the plugin based nature of the Avogadro project many specialized options can be added, such as raytracing the electronic structure of the molecule to produce high quality output, building carbon nanotube structures, or designing solid-state structures. Avogadro is already being used by educators and researchers. Due to the free and open source nature of the project, it can be readily downloaded and used by all students in and out of the classroom. It can also be tailored to particular institutions and/or courses.

  19. a New Hybrid Program for Fitting Rotationally Resolved Spectra of Methylamine-Like Molecules: Application to 2-METHYLMALONALDEHYDE

    NASA Astrophysics Data System (ADS)

    Kleiner, Isabelle; Hougen, Jon T.

    2015-06-01

    A new hybrid-model fitting program for methylamine-like molecules has been developed, based on an effective Hamiltonian in which the ammonia-like inversion motion is treated using a tunneling formalism, while the internal-rotation motion is treated using an explicit kinetic energy operator and potential energy function. The Hamiltonian in the computer program is set up as a 2x2 partitioned matrix, where each diagonal block consists of a traditional torsion-rotation Hamiltonian (as in the earlier program BELGI), and the two off-diagonal blocks contain all tunneling terms. This hybrid formulation permits the use of the permutation-inversion group G6 (isomorphic to C3v) for terms in the two diagonal blocks, but requires G12 for terms in the off-diagonal blocks. Our first application of the new program is to 2-methylmalonaldehyde. Microwave data for this molecule were previously fit (essentially to experimental measurement error) using an all-tunneling Hamiltonian formalism to treat both large-amplitude-motions. For 2-methylmalonaldehyde, the hybrid program achieves a fit of nearly the same quality as that obtained by the all-tunneling program, but fits with the hybrid program eliminate a large discrepancy between internal rotation barriers in the OH and OD isotopologues of 2-methylmalonaldehyde that arose in fits with the all-tunneling program. Other molecules for application of the hybrid program will be mentioned. V.V. Ilyushin, E.A. Alekseev, Yung-Ching Chou, Yen-Chu Hsu, J. T. Hougen, F.J. Lovas, L. Picraux, J. Mol. Spectrosc. 251 (2008) 56-63

  20. ATIRS package: A program suite for the rovibrational analysis of infrared spectra of asymmetric top molecules

    NASA Astrophysics Data System (ADS)

    Tasinato, N.; Pietropolli Charmet, A.; Stoppa, P.

    2007-06-01

    Nowadays high-resolution infrared spectra can be recorded quite easily and therefore it has become important to assist the rovibrational analysis, especially the assignment step, that is still fraught with many problems in the presence of perturbation effects. In this article we provide a description of ATIRS, a complete software suite developed for assisting in the rotational investigation of vibrational bands of asymmetric top molecules. This package uses the Pickett's CALPGM suite for fitting transitions and predicting line positions and is composed by three stand-alone applications: (1) Visual Loomis-Wood for the assignment of spectral lines based on Loomis-Wood type diagrams; (2) Visual CALPGM, a new graphical interface to Pickett's programs SPFIT and SPCAT; (3) Visual Spectra Simulator for the simulation of spectra. The graphical interface to the CALPGM suite is developed for asymmetric rotors. The main feature of this application is to avoid the use of the parameter codes that are here replaced employing the well known parameter names or symbols. Highlighting the regular transition sequences, Visual Loomis-Wood assists in the assignment of the spectral lines. It visualizes the description of a transition and the assignment can be simply done by mouse-clicking on the diagram; moreover its display mode feature lets to check the experimental spectrum in which all the assigned lines together with their description are reported. Visual Spectra Simulator provides a simple and functionally application that, using the calculated frequencies and intensities given by SPCAT, simulates the high-resolution infrared spectrum and compare it to the experimental one. ATIRS, freely available to the spectroscopic community, is designed to be easy to use and presents a standard graphical interface; being based on the CALPGM package it can handle forbidden transitions and perturbations among many states.

  1. A computer program for a line-by-line calculation of spectra from diatomic molecules and atoms assuming a Voight line profile

    NASA Technical Reports Server (NTRS)

    Arnold, J. O.; Lyle, G. C.; Whiting, E. E.

    1969-01-01

    Computer program predicts the spectra resulting from electronic transitions of diatomic molecules and atoms in local thermodynamic equilibrium. The program produces a spectrum by accounting for the contribution of each rotational and atomic line considered.

  2. Isomer-Selective Detection of Aromatic Molecules in Temperature-Programmed Desorption for Model Catalysis.

    PubMed

    Winbauer, Andreas; Kollmannsberger, Sebastian L; Walenta, Constantin A; Schreiber, Patrick; Kiermaier, Josef; Tschurl, Martin; Heiz, Ueli

    2016-05-17

    Based on three different molecules dosed on a Pt(111) single crystal the selectivity and sensitivity of REMPI-TPD in UHV is investigated for a potential application in heterogeneous catalysis. It is shown that the two structural isomers ethylbenzene and p-xylene can be discriminated by REMPI in a standard TPD experiment. The latter is not possible for the ionization with electrons in a Q-MS. It is further demonstrated by benzene TPD studies that the sensitivity of the REMPI-TOF-MS is comparable to commercial EI-Q-MS solutions and enables the detection of less than 0.6% molecules of a monolayer. PMID:27078611

  3. Suppression of the FOXM1 transcriptional program via novel small molecule inhibition

    PubMed Central

    Gormally, Michael V.; Dexheimer, Thomas S.; Marsico, Giovanni; Sanders, Deborah A.; Lowe, Christopher; Matak-Vinkovi, Dijana; Michael, Sam; Jadhav, Ajit; Rai, Ganesha; Maloney, David J.; Simeonov, Anton; Balasubramanian, Shankar

    2014-01-01

    The transcription factor FOXM1 binds to sequence-specific motifs on DNA (C/TAAACA) through its DNA binding domain (DBD), and activates proliferation- and differentiation-associated genes. Aberrant overexpression of FOXM1 is a key feature in oncogenesis and progression of many human cancers. Here — from a high-throughput screen applied to a library of 54,211 small molecules — we identify novel small molecule inhibitors of FOXM1 that block DNA binding. One of the identified compounds: FDI-6 (NCGC00099374) is characterized in depth and is shown to bind directly to FOXM1 protein, to displace FOXM1 from genomic targets in MCF-7 breast cancer cells, and induce concomitant transcriptional down-regulation. Global transcript profiling of MCF-7 cells by RNA-seq shows that FDI-6 specifically down regulates FOXM1-activated genes with FOXM1 occupancy confirmed by ChIP-seq. This small molecule mediated effect is selective for FOXM1-controlled genes with no effect on genes regulated by homologous forkhead family factors. PMID:25387393

  4. Interaction between water molecules and zinc sulfide nanoparticles studied by temperature-programmed desorption and molecular dynamics simulations.

    PubMed

    Zhang, Hengzhong; Rustad, James R; Banfield, Jillian F

    2007-06-14

    We have investigated the bonding of water molecules to the surfaces of ZnS nanoparticles (approximately 2-3 nm sphalerite) using temperature-programmed desorption (TPD). The activation energy for water desorption was derived as a function of the surface coverage through kinetic modeling of the experimental TPD curves. The binding energy of water equals the activation energy of desorption if it is assumed that the activation energy for adsorption is nearly zero. Molecular dynamics (MD) simulations of water adsorption on 3 and 5 nm sphalerite nanoparticles provided insights into the adsorption process and water binding at the atomic level. Water binds with the ZnS nanoparticle surface mainly via formation of Zn-O bonds. As compared with bulk ZnS crystals, ZnS nanoparticles can adsorb more water molecules per unit surface area due to the greatly increased curvature, which increases the distance between adjacent adsorbed molecules. Results from both TPD and MD show that the water binding energy increases with decreasing the water surface coverage. We attribute the increase in binding energy with decreasing surface water coverage to the increasing degree of surface under-coordination as removal of water molecules proceeds. MD also suggests that the water binding energy increases with decreasing particle size due to the further distance and hence lower interaction between adsorbed water molecules on highly curved smaller particle surfaces. Results also show that the binding energy, and thus the strength of interaction of water, is highest in isolated nanoparticles, lower in nanoparticle aggregates, and lowest in bulk crystals. Given that water binding is driven by surface energy reduction, we attribute the decreased binding energy for aggregated as compared to isolated particles to the decrease in surface energy that occurs as the result of inter-particle interactions. PMID:17518448

  5. Computer program for determining rotational line intensity factors for diatomic molecules

    NASA Technical Reports Server (NTRS)

    Whiting, E. E.

    1973-01-01

    A FORTRAN IV computer program, that provides a new research tool for determining reliable rotational line intensity factors (also known as Honl-London factors), for most electric and magnetic dipole allowed diatomic transitions, is described in detail. This users manual includes instructions for preparing the input data, a program listing, detailed flow charts, and three sample cases. The program is applicable to spin-allowed dipole transitions with either or both states intermediate between Hund's case (a) and Hund's case (b) coupling and to spin-forbidden dipole transitions with either or both states intermediate between Hund's case (c) and Hund's case (b) coupling.

  6. Modeling Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

  7. Theoretical research program to predict the properties of molecules and clusters containing transition metal atoms

    NASA Technical Reports Server (NTRS)

    Walch, S.

    1984-01-01

    The primary focus of this research has been the theoretical study of transition metal (TM) chemistry. A major goal of this work is to provide reliable information about the interaction of H atoms with iron metal. This information is needed to understand the effect of H atoms on the processes of embrittlement and crack propagation in iron. The method in the iron hydrogen studies is the cluster method in which the bulk metal is modelled by a finite number of iron atoms. There are several difficulties in the application of this approach to the hydrogen iron system. First the nature of TM-TM and TM-H bonding for even diatomic molecules was not well understood when these studies were started. Secondly relatively large iron clusters are needed to provide reasonable results.

  8. Programmed Lab Experiments for Biochemical Investigation of Quorum-Sensing Signal Molecules in Rhizospheric Soil Bacteria

    ERIC Educational Resources Information Center

    Nievas, Fiorela L.; Bogino, Pablo C.; Giordano, Walter

    2016-01-01

    Biochemistry courses in the Department of Molecular Biology at the National University of Río Cuarto, Argentina, are designed for undergraduate students in biology, microbiology, chemistry, agronomy, and veterinary medicine. Microbiology students typically have previous coursework in general, analytical, and organic chemistry. Programmed sequences…

  9. MSTor: A program for calculating partition functions, free energies, enthalpies, entropies, and heat capacities of complex molecules including torsional anharmonicity

    NASA Astrophysics Data System (ADS)

    Zheng, Jingjing; Mielke, Steven L.; Clarkson, Kenneth L.; Truhlar, Donald G.

    2012-08-01

    We present a Fortran program package, MSTor, which calculates partition functions and thermodynamic functions of complex molecules involving multiple torsional motions by the recently proposed MS-T method. This method interpolates between the local harmonic approximation in the low-temperature limit, and the limit of free internal rotation of all torsions at high temperature. The program can also carry out calculations in the multiple-structure local harmonic approximation. The program package also includes six utility codes that can be used as stand-alone programs to calculate reduced moment of inertia matrices by the method of Kilpatrick and Pitzer, to generate conformational structures, to calculate, either analytically or by Monte Carlo sampling, volumes for torsional subdomains defined by Voronoi tessellation of the conformational subspace, to generate template input files, and to calculate one-dimensional torsional partition functions using the torsional eigenvalue summation method. Catalogue identifier: AEMF_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEMF_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 77 434 No. of bytes in distributed program, including test data, etc.: 3 264 737 Distribution format: tar.gz Programming language: Fortran 90, C, and Perl Computer: Itasca (HP Linux cluster, each node has two-socket, quad-core 2.8 GHz Intel Xeon X5560 “Nehalem EP” processors), Calhoun (SGI Altix XE 1300 cluster, each node containing two quad-core 2.66 GHz Intel Xeon “Clovertown”-class processors sharing 16 GB of main memory), Koronis (Altix UV 1000 server with 190 6-core Intel Xeon X7542 “Westmere” processors at 2.66 GHz), Elmo (Sun Fire X4600 Linux cluster with AMD Opteron cores), and Mac Pro (two 2.8 GHz Quad-core Intel Xeon

  10. Perinatal programming of emotional brain circuits: an integrative view from systems to molecules

    PubMed Central

    Bock, Jörg; Rether, Kathy; Gröger, Nicole; Xie, Lan; Braun, Katharina

    2014-01-01

    Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional “scars” in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of “stress inoculation” is emerging from more recent research, which revealed positive functional adaptations in response to ELS resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life. PMID:24550772

  11. Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A.

    PubMed

    Zhao, Qunfei; Wang, Min; Xu, Dongxiao; Zhang, Qinglin; Liu, Wen

    2015-02-01

    Low-molecular-mass thiols in organisms are well known for their redox-relevant role in protection against various endogenous and exogenous stresses. In eukaryotes and Gram-negative bacteria, the primary thiol is glutathione (GSH), a cysteinyl-containing tripeptide. In contrast, mycothiol (MSH), a cysteinyl pseudo-disaccharide, is dominant in Gram-positive actinobacteria, including antibiotic-producing actinomycetes and pathogenic mycobacteria. MSH is equivalent to GSH, either as a cofactor or as a substrate, in numerous biochemical processes, most of which have not been characterized, largely due to the dearth of information concerning MSH-dependent proteins. Actinomycetes are able to produce another thiol, ergothioneine (EGT), a histidine betaine derivative that is widely assimilated by plants and animals for variable physiological activities. The involvement of EGT in enzymatic reactions, however, lacks any precedent. Here we report that the unprecedented coupling of two bacterial thiols, MSH and EGT, has a constructive role in the biosynthesis of lincomycin A, a sulfur-containing lincosamide (C8 sugar) antibiotic that has been widely used for half a century to treat Gram-positive bacterial infections. EGT acts as a carrier to template the molecular assembly, and MSH is the sulfur donor for lincomycin maturation after thiol exchange. These thiols function through two unusual S-glycosylations that program lincosamide transfer, activation and modification, providing the first paradigm for EGT-associated biochemical processes and for the poorly understood MSH-dependent biotransformations, a newly described model that is potentially common in the incorporation of sulfur, an element essential for life and ubiquitous in living systems. PMID:25607359

  12. Classification of drug molecules considering their IC50 values using mixed-integer linear programming based hyper-boxes method

    PubMed Central

    Armutlu, Pelin; Ozdemir, Muhittin E; Uney-Yuksektepe, Fadime; Kavakli, I Halil; Turkay, Metin

    2008-01-01

    Background A priori analysis of the activity of drugs on the target protein by computational approaches can be useful in narrowing down drug candidates for further experimental tests. Currently, there are a large number of computational methods that predict the activity of drugs on proteins. In this study, we approach the activity prediction problem as a classification problem and, we aim to improve the classification accuracy by introducing an algorithm that combines partial least squares regression with mixed-integer programming based hyper-boxes classification method, where drug molecules are classified as low active or high active regarding their binding activity (IC50 values) on target proteins. We also aim to determine the most significant molecular descriptors for the drug molecules. Results We first apply our approach by analyzing the activities of widely known inhibitor datasets including Acetylcholinesterase (ACHE), Benzodiazepine Receptor (BZR), Dihydrofolate Reductase (DHFR), Cyclooxygenase-2 (COX-2) with known IC50 values. The results at this stage proved that our approach consistently gives better classification accuracies compared to 63 other reported classification methods such as SVM, Naïve Bayes, where we were able to predict the experimentally determined IC50 values with a worst case accuracy of 96%. To further test applicability of this approach we first created dataset for Cytochrome P450 C17 inhibitors and then predicted their activities with 100% accuracy. Conclusion Our results indicate that this approach can be utilized to predict the inhibitory effects of inhibitors based on their molecular descriptors. This approach will not only enhance drug discovery process, but also save time and resources committed. PMID:18834515

  13. Defective Tapetum Cell Death 1 (DTC1) Regulates ROS Levels by Binding to Metallothionein during Tapetum Degeneration.

    PubMed

    Yi, Jakyung; Moon, Sunok; Lee, Yang-Seok; Zhu, Lu; Liang, Wanqi; Zhang, Dabing; Jung, Ki-Hong; An, Gynheung

    2016-03-01

    After meiosis, tapetal cells in the innermost anther wall layer undergo program cell death (PCD)-triggered degradation. This step is essential for microspore development and pollen wall maturation. We identified a key gene, Defective Tapetum Cell Death 1 (DTC1), that controls this degeneration by modulating the dynamics of reactive oxygen species (ROS) during rice male reproduction. Mutants defective in DTC1 exhibit phenotypes of an enlarged tapetum and middle layer with delayed degeneration, causing male sterility. The gene is preferentially expressed in the tapetal cells during early anther development. In dtc1 anthers, expression of genes encoding secretory proteases or lipid transporters is significantly reduced, while transcripts of PCD regulatory genes, e.g. UDT1, TDR1, and EAT1/DTD, are not altered. Moreover, levels of DTC1 transcripts are diminished in udt1, tdr, and eat1 anthers. These results suggest that DTC1 functions downstream of those transcription factor genes and upstream of the genes encoding secretory proteins. DTC1 protein interacts with OsMT2b, a ROS scavenger. Whereas wild-type plants accumulate large amounts of ROS in their anthers at Stage 9 of development, those levels remain low during all stages of development in dtc1 anthers. These findings indicate that DTC1 is a key regulator for tapetum PCD by inhibiting ROS-scavenging activity. PMID:26697896

  14. Defective Tapetum Cell Death 1 (DTC1) Regulates ROS Levels by Binding to Metallothionein during Tapetum Degeneration1[OPEN

    PubMed Central

    Moon, Sunok; Lee, Yang-Seok; Zhu, Lu; Jung, Ki-Hong; An, Gynheung

    2016-01-01

    After meiosis, tapetal cells in the innermost anther wall layer undergo program cell death (PCD)-triggered degradation. This step is essential for microspore development and pollen wall maturation. We identified a key gene, Defective Tapetum Cell Death 1 (DTC1), that controls this degeneration by modulating the dynamics of reactive oxygen species (ROS) during rice male reproduction. Mutants defective in DTC1 exhibit phenotypes of an enlarged tapetum and middle layer with delayed degeneration, causing male sterility. The gene is preferentially expressed in the tapetal cells during early anther development. In dtc1 anthers, expression of genes encoding secretory proteases or lipid transporters is significantly reduced, while transcripts of PCD regulatory genes, e.g. UDT1, TDR1, and EAT1/DTD, are not altered. Moreover, levels of DTC1 transcripts are diminished in udt1, tdr, and eat1 anthers. These results suggest that DTC1 functions downstream of those transcription factor genes and upstream of the genes encoding secretory proteins. DTC1 protein interacts with OsMT2b, a ROS scavenger. Whereas wild-type plants accumulate large amounts of ROS in their anthers at Stage 9 of development, those levels remain low during all stages of development in dtc1 anthers. These findings indicate that DTC1 is a key regulator for tapetum PCD by inhibiting ROS-scavenging activity. PMID:26697896

  15. Molecule nanoweaver

    DOEpatents

    Gerald, II; Rex E.; Klingler, Robert J.; Rathke, Jerome W.; Diaz, Rocio; Vukovic, Lela

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  16. Comprehensive Analysis of the Therapeutic IgG4 Antibody Pembrolizumab: Hinge Modification Blocks Half Molecule Exchange In Vitro and In Vivo.

    PubMed

    Yang, Xiaoyu; Wang, Fengqiang; Zhang, Ying; Wang, Larry; Antonenko, Svetlana; Zhang, Shuli; Zhang, Yi Wei; Tabrizifard, Mohammad; Ermakov, Grigori; Wiswell, Derek; Beaumont, Maribel; Liu, Liming; Richardson, Daisy; Shameem, Mohammed; Ambrogelly, Alexandre

    2015-12-01

    IgG4 antibodies are evolving as an important class of cancer immunotherapies. However, human IgG4 can undergo Fab arm (half molecule) exchange with other IgG4 molecules in vivo. The hinge modification by a point mutation (S228P) prevents half molecule exchange of IgG4. However, the experimental confirmation is still expected by regulatory agencies. Here, we report for the first time the extensive analysis of half molecule exchange for a hinge-modified therapeutic IgG4 molecule, pembrolizumab (Keytruda) targeting programmed death 1 (PD1) receptor that was approved for advanced melanoma. Studies were performed in buffer or human serum using multiple exchange partners including natalizumab (Tysabri) and human IgG4 pool. Formation of bispecific antibodies was monitored by fluorescence resonance energy transfer, exchange with Fc fragments, mixed mode chromatography, immunoassays, and liquid chromatography-mass spectrometry. The half molecule exchange was also examined in vivo in SCID (severe combined immunodeficiency) mice. Both in vitro and in vivo results indicate that the hinge modification in pembrolizumab prevented half molecule exchange, whereas the unmodified counterpart anti-PD1 wt showed active exchange activity with other IgG4 antibodies or self-exchange activity with its own molecules. Our work, as an example expected for meeting regulatory requirements, contributes to establish without ambiguity that hinge-modified IgG4 antibodies are suitable for biotherapeutic applications. PMID:26308749

  17. Efficient and accurate determination of the overall rotational diffusion tensor of a molecule from 15N relaxation data using computer program ROTDIF

    NASA Astrophysics Data System (ADS)

    Walker, Olivier; Varadan, Ranjani; Fushman, David

    2004-06-01

    We present a computer program ROTDIF for efficient determination of a complete rotational diffusion tensor of a molecule from NMR relaxation data. The derivation of the rotational diffusion tensor in the case of a fully anisotropic model is based on a six-dimensional search, which could be very time consuming, particularly if a grid search in the Euler angle space is involved. Here, we use an efficient Levenberg-Marquardt algorithm combined with Monte Carlo generation of initial guesses. The result is a dramatic, up to 50-fold improvement in the computational efficiency over the previous approaches [Biochemistry 38 (1999) 10225; J. Magn. Reson. 149 (2001) 214]. This method is demonstrated on a computer-generated and real protein systems. We also address the issue of sensitivity of the diffusion tensor determination from 15N relaxation measurements to experimental errors in the relaxation rates and discuss possible artifacts from applying higher-symmetry tensor model and how to recognize them.

  18. Investigation of the distribution of acidity strength in zeolites by temperature-programmed desorption of probe molecules. 2. Dealuminated Y-type zeolites

    SciTech Connect

    Karge, H.G.; Dondur, V. ); Weitkamp, J. )

    1991-01-10

    The acidity of dealuminated hydrogen forms of Y-type zeolites (Si/Al = 2.4-8.6) is determined by temperature-programmed desorption of ammonia or pyridine, which is monitored through a mass spectrometer. Four types of acidic sites are indicated by ammonia, viz., weak Broensted and/or Lewis centers and medium and strong Broensted and strong Lewis sites. In contrast, pyridine, after sample activation at 675 K, probed only two types of sites, i.e., medium and strong Broensted sites. This difference is ascribed to different accessibility of sites for the two probe molecules. From the desorption spectra (i) the fractional coverage of the various sites, (ii) the most frequent energies of activation, {anti E}{sub d}, for desorption, and (iii) the probability functions of the activation energies are derived by using a previously described method of evaluation.

  19. Interstellar molecules

    NASA Astrophysics Data System (ADS)

    Smith, D.

    1987-09-01

    Some 70 different molecular species have so far been detected variously in diffuse interstellar clouds, dense interstellar clouds, and circumstellar shells. Only simple (diatomic and triatomic) species exist in diffuse clouds because of the penetration of destructive UV radiations, whereas more complex (polyatomic) molecules survive in dense clouds as a result of the shielding against this UV radiation provided by dust grains. A current list of interstellar molecules is given together with a few other molecular species that have so far been detected only in circumstellar shells. Also listed are those interstellar species that contain rare isotopes of several elements. The gas phase ion chemistry is outlined via which the observed molecules are synthesized, and the process by which enrichment of the rare isotopes occurs in some interstellar molecules is described.

  20. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  1. Dehydroascorbate: a possible surveillance molecule of oxidative stress and programmed cell death in the green alga Chlamydomonas reinhardtii.

    PubMed

    Murik, Omer; Elboher, Ahinoam; Kaplan, Aaron

    2014-04-01

    Chlamydomonas reinhardtii tolerates relatively high H2 O2 levels that induce an array of antioxidant activities. However, rather than rendering the cells more resistant to oxidative stress, the cells become far more sensitive to an additional H2 O2 dose. If H2 O2 is provided 1.5-9 h after an initial dose, it induces programmed cell death (PCD) in the wild-type, but not in the dum1 mutant impaired in the mitochondrial respiratory complex III. This mutant does not exhibit a secondary oxidative burst 4-5 h after the inducing H2 O2 , nor does it activate metacaspase-1 after the second H2 O2 treatment. The intracellular dehydroascorbate level, a product of ascorbate peroxidase, increases under conditions leading to PCD. The addition of dehydroascorbate induces PCD in the wild-type and dum1 cultures, but higher levels are required in dum1 cells, where it is metabolized faster. The application of dehydroascorbate induces the expression of metacaspase-2, which is much stronger than the expression of metacaspase-1. The presence or absence of oxidative stress, in addition to the rise in internal dehydroascorbate, may determine which metacaspase is activated during Chlamydomonas PCD. Cell death is strongly affected by the timing of H2 O2 or dehydroascorbate admission to synchronously grown cultures, suggesting that the cell cycle phase may distinguish cells that perish from those that do not. PMID:24345283

  2. Enumerating molecules.

    SciTech Connect

    Visco, Donald Patrick, Jr.; Faulon, Jean-Loup Michel; Roe, Diana C.

    2004-04-01

    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

  3. Immunoregulatory molecules are master regulators of inflammation during the immune response

    PubMed Central

    Sánchez-Madrid, Francisco

    2014-01-01

    The balance between pro- and anti-inflammatory signalling is critical to maintain the immune homeostasis under physiological conditions as well as for the control of inflammation in different pathological settings. Recent progress in the signalling pathways that control this balance has led to the development of novel therapeutic agents for diseases characterized by alterations in the activation/suppression of the immune response. Different molecules have a key role in the regulation of the immune system, including the receptors PD-1 (Programmed cell Death 1), CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4) and galectins; or the intracellular enzyme IDO (indoleamine 2,3-dioxygenase). In addition, other molecules as CD69, AhR (Aryl hydrocarbon Receptor), and GADD45 (Growth Arrest and DNA Damage-inducible 45) family members, have emerged as potential targets for the regulation of the activation/suppression balance of immune cells. This review offers a perspective on well-characterized as well as emergent negative immune regulatory molecules in the context of autoimmune inflammatory diseases. PMID:22819828

  4. Mind Molecules

    PubMed Central

    Snyder, Solomon H.

    2011-01-01

    Scientific styles vary tremendously. For me, research is largely about the unfettered pursuit of novel ideas and experiments that can test multiple ideas in a day, not a year, an approach that I learned from my mentor Julius “Julie” Axelrod. This focus on creative conceptualizations has been my métier since working in the summers during medical school at the National Institutes of Health, during my two years in the Axelrod laboratory, and throughout my forty-five years at Johns Hopkins University School of Medicine. Equally important has been the “high” that emerges from brainstorming with my students. Nothing can compare with the eureka moments when, together, we sense new insights and, better yet, when high-risk, high-payoff experiments succeed. Although I have studied many different questions over the years, a common theme emerges: simple biochemical approaches to understanding molecular messengers, usually small molecules. Equally important has been identifying, purifying, and cloning the messengers' relevant biosynthetic, degradative, or target proteins, at all times seeking potential therapeutic relevance in the form of drugs. In the interests of brevity, this Reflections article is highly selective, and, with a few exceptions, literature citations are only of findings of our laboratory that illustrate notable themes. PMID:21543333

  5. Relative Sizes of Organic Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This computer graphic depicts the relative complexity of crystallizing large proteins in order to study their structures through x-ray crystallography. Insulin is a vital protein whose structure has several subtle points that scientists are still trying to determine. Large molecules such as insuline are complex with structures that are comparatively difficult to understand. For comparison, a sugar molecule (which many people have grown as hard crystals in science glass) and a water molecule are shown. These images were produced with the Macmolecule program. Photo credit: NASA/Marshall Space Flight Center (MSFC)

  6. Distinct effects of human glioblastoma immunoregulatory molecules programmed cell death ligand-1 (PDL-1) and indoleamine 2,3-dioxygenase (IDO) on tumour-specific T cell functions.

    PubMed

    Avril, Tony; Saikali, Stéphan; Vauleon, Elodie; Jary, Anne; Hamlat, Abderrahmane; De Tayrac, Marie; Mosser, Jean; Quillien, Véronique

    2010-08-25

    Immunotherapy is a promising new treatment for patients suffering from glioma, in particular glioblastoma multiforme (GBM). However, tumour cells use different mechanisms to escape the immune responses induced by the treatment. As many other tumours, gliomas express or secrete several immunosuppressive molecules that regulate immune cell functions. In this study, we first analysed FasL, HLA-G, IDO, PDL-1 and TGF-beta1, -beta2 and -beta3 expression by transcriptomic microarray analysis in a series of 20 GBM samples and found respectively 15%, 60%, 85%, 30%, 70%, 80% and 35% of positive specimens. mRNA expression was then confirmed in 10 GBM primary cell lines and 2 immortalised cell lines U251 and U87MG. Furthermore, the protein expression of PDL-1, IDO activity and TGF-beta2 secretion were found on most of the untreated GBM primary cell lines. Remarkably, treatment with IFN-gamma increased the PDL-1 cell surface expression and the IDO activity, but reduced the TGF-beta2 secretion of GBM cell lines. We finally analysed the immunosuppressive effects of IDO, PDL-1 and TGF-beta1-3 by measuring IFN-gamma production and cell cytotoxicity activity of tumour antigen-specific T cells. PDL-1 partially affected the IFN-gamma production of antigen-specific T cells in response to GBM primary cell lines, and IDO inhibited lymphocyte proliferation induced by lectins. None of these molecules directly affected the T cell cytotoxicity function. Due to the functional role of PDL-1 and IDO molecules expressed by GBM cells, one could expect that blocking these molecules in the immunotherapy strategies would reinforce the efficiency of these treatments of GBM patients. PMID:20493562

  7. Small molecule-directed specification of sclerotome-like chondroprogenitors and induction of a somitic chondrogenesis program from embryonic stem cells.

    PubMed

    Zhao, Jiangang; Li, Songhui; Trilok, Suprita; Tanaka, Makoto; Jokubaitis-Jameson, Vanta; Wang, Bei; Niwa, Hitoshi; Nakayama, Naoki

    2014-10-01

    Pluripotent embryonic stem cells (ESCs) generate rostral paraxial mesoderm-like progeny in 5-6 days of differentiation induced by Wnt3a and Noggin (Nog). We report that canonical Wnt signaling introduced either by forced expression of activated β-catenin, or the small-molecule inhibitor of Gsk3, CHIR99021, satisfied the need for Wnt3a signaling, and that the small-molecule inhibitor of BMP type I receptors, LDN193189, was able to replace Nog. Mesodermal progeny generated using such small molecules were chondrogenic in vitro, and expressed trunk paraxial mesoderm markers such as Tcf15 and Meox1, and somite markers such as Uncx, but failed to express sclerotome markers such as Pax1. Induction of the osteochondrogenically committed sclerotome from somite requires sonic hedgehog and Nog. Consistently, Pax1 and Bapx1 expression was induced when the isolated paraxial mesodermal progeny were treated with SAG1 (a hedgehog receptor agonist) and LDN193189, then Sox9 expression was induced, leading to cartilaginous nodules and particles in the presence of BMP, indicative of chondrogenesis via sclerotome specification. By contrast, treatment with TGFβ also supported chondrogenesis and stimulated Sox9 expression, but failed to induce the expression of Pax1 and Bapx1. On ectopic transplantation to immunocompromised mice, the cartilage particles developed under either condition became similarly mineralized and formed pieces of bone with marrow. Thus, the use of small molecules led to the effective generation from ESCs of paraxial mesodermal progeny, and to their further differentiation in vitro through sclerotome specification into growth plate-like chondrocytes, a mechanism resembling in vivo somitic chondrogenesis that is not recapitulated with TGFβ. PMID:25294938

  8. Programs.

    ERIC Educational Resources Information Center

    Community College Journal, 1996

    1996-01-01

    Includes a collection of eight short articles describing model community college programs. Discusses a literacy program, a mobile computer classroom, a support program for at-risk students, a timber-harvesting program, a multimedia presentation on successful women graduates, a career center, a collaboration with NASA, and an Israeli engineering…

  9. Physics of Molecules

    NASA Astrophysics Data System (ADS)

    Williams, D.; Murdin, P.

    2000-11-01

    Many varieties of molecule have been detected in the Milky Way and in other galaxies. The processes by which these molecules are formed and destroyed are now broadly understood (see INTERSTELLAR CHEMISTRY). These molecules are important components of galaxies in two ways. Firstly, radiation emitted by molecules enables us to trace the presence of diffuse gas, to infer its physical properties and ...

  10. Singlet Oxygen-Induced Membrane Disruption and Serpin-Protease Balance in Vacuolar-Driven Cell Death1[OPEN

    PubMed Central

    Carmieli, Raanan; Mor, Avishai; Fluhr, Robert

    2016-01-01

    Singlet oxygen plays a role in cellular stress either by providing direct toxicity or through signaling to initiate death programs. It was therefore of interest to examine cell death, as occurs in Arabidopsis, due to differentially localized singlet oxygen photosensitizers. The photosensitizers rose bengal (RB) and acridine orange (AO) were localized to the plasmalemma and vacuole, respectively. Their photoactivation led to cell death as measured by ion leakage. Cell death could be inhibited by the singlet oxygen scavenger histidine in treatments with AO but not with RB. In the case of AO treatment, the vacuolar membrane was observed to disintegrate. Concomitantly, a complex was formed between a vacuolar cell-death protease, RESPONSIVE TO DESSICATION-21 and its cognate cytoplasmic protease inhibitor ATSERPIN1. In the case of RB treatment, the tonoplast remained intact and no complex was formed. Over-expression of AtSerpin1 repressed cell death, only under AO photodynamic treatment. Interestingly, acute water stress showed accumulation of singlet oxygen as determined by fluorescence of Singlet Oxygen Sensor Green, by electron paramagnetic resonance spectroscopy and the induction of singlet oxygen marker genes. Cell death by acute water stress was inhibited by the singlet oxygen scavenger histidine and was accompanied by vacuolar collapse and the appearance of serpin-protease complex. Over-expression of AtSerpin1 also attenuated cell death under this mode of cell stress. Thus, acute water stress damage shows parallels to vacuole-mediated cell death where the generation of singlet oxygen may play a role. PMID:26884487

  11. A fitting program for molecules with two equivalent methyl tops and C2v point-group symmetry at equilibrium: Application to existing microwave, millimeter, and sub-millimeter wave measurements of acetone

    NASA Astrophysics Data System (ADS)

    Ilyushin, Vadim V.; Hougen, Jon. T.

    2013-07-01

    A program, called PAM_C2v_2tops, for fitting the high-resolution torsion-rotation spectra of molecules with two equivalent methyl rotors and C2v symmetry at equilibrium is described and applied to the spectrum of acetone [(CH3)2CO]. The G36 permutation-inversion group-theoretical considerations used in the design of the program are presented followed by a description of the structure of the program, which uses the principal axis method and a two-step diagonalization procedure. The program was used to carry out a weighted least-squares fit of 1720 microwave, millimeter-wave, and sub-millimeter-wave line frequencies of acetone that are available in the literature. The weighted standard deviation of 0.94 obtained here for a joint fit of rotational lines belonging to the ground, the lower torsional fundamental, and the higher torsional fundamental states of acetone represents significant progress in comparison with previous fitting attempts, especially for the excited torsional states.

  12. Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I.

    PubMed

    Boudreau, Jeanette E; Liu, Xiao-Rong; Zhao, Zeguo; Zhang, Aaron; Shultz, Leonard D; Greiner, Dale L; Dupont, Bo; Hsu, Katharine C

    2016-08-16

    The effector potential of NK cells is counterbalanced by their sensitivity to inhibition by "self" MHC class I molecules in a process called "education." In humans, interactions between inhibitory killer immunoglobulin-like receptors (KIR) and human MHC (HLA) mediate NK cell education. In HLA-B(∗)27:05(+) transgenic mice and in patients undergoing HLA-mismatched hematopoietic cell transplantation (HCT), NK cells derived from human CD34(+) stem cells were educated by HLA from both donor hematopoietic cells and host stromal cells. Furthermore, mature human KIR3DL1(+) NK cells gained reactivity after adoptive transfer to HLA-B(∗)27:05(+) mice or bone marrow chimeric mice where HLA-B(∗)27:05 was restricted to either the hematopoietic or stromal compartment. Silencing of HLA in primary NK cells diminished NK cell reactivity, while acquisition of HLA from neighboring cells increased NK cell reactivity. Altogether, these findings reveal roles for cell-extrinsic HLA in driving NK cell reactivity upward, and cell-intrinsic HLA in maintaining NK cell education. PMID:27496730

  13. Engineering biological systems with synthetic RNA molecules

    PubMed Central

    Liang, Joe C.; Bloom, Ryan J.; Smolke, Christina D.

    2011-01-01

    RNA molecules play diverse functional roles in natural biological systems. There has been growing interest in designing synthetic RNA counterparts for programming biological function. The design of synthetic RNA molecules that exhibit diverse activities, including sensing, regulatory, information processing, and scaffolding activities, has highlighted the advantages of RNA as a programmable design substrate. Recent advances in implementing these engineered RNA molecules as key control elements in synthetic genetic networks are highlighting the functional relevance of this class of synthetic elements in programming cellular behaviors. PMID:21925380

  14. Evaluation of Costimulatory Molecules in Peripheral Blood Lymphocytes of Canine Patients with Histiocytic Sarcoma

    PubMed Central

    Tagawa, Michihito; Maekawa, Naoya; Konnai, Satoru; Takagi, Satoshi

    2016-01-01

    Histiocytic sarcoma is a rapidly progressive and fatal neoplastic disease in dogs. It is unclear whether costimulatory molecules, including CD28, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and programmed death-1 (PD-1), are expressed on peripheral blood lymphocytes (PBLs) of canine patients with histiocytic sarcoma. The objective of this study was to evaluate the expression of CD28, CTLA-4, and PD-1 molecules on PBLs of patients with histiocytic sarcoma, patients with other tumors, and healthy controls. Twenty-six dogs were included in the study, with eight, ten, and eight dogs in the histiocytic sarcoma, other tumor, and healthy control groups, respectively. PBLs and serum were prospectively obtained from patients diagnosed histopathologically with histiocytic sarcoma, other tumors and healthy controls. The surface expression of CTLA-4, CD28, and PD-1 on T lymphocytes was examined using flow cytometric analysis. Serum samples were frozen at −30°C until serum interferon-γ (IFN-γ) was measured by enzyme-linked immunosorbent assay. The expression level of CTLA-4 on CD4+ lymphocytes was significantly higher in the histiocytic sarcoma group than in the control group. The expression of CTLA-4 on CD8+ lymphocytes was significantly higher in the histiocytic sarcoma group than in the other two groups. In addition, the expression of PD-1 on CD8+ lymphocytes was significantly higher in the histiocytic sarcoma group than in the control group. However, no significant differences in CD28 expressions and serum IFN-γ levels were observed. The present results provided evidence showing that the expression levels of CTLA-4 on both CD4+ and CD8+ lymphocytes and PD-1 on CD8+ lymphocytes in peripheral blood obtained from dogs with histiocytic sarcoma were upregulated. The overexpressions of CTLA 4 and PD-1 suggested that antitumor immunity may be suppressed in dogs with histiocytic sarcoma. PMID:26901565

  15. Engineering crystals of dendritic molecules.

    PubMed

    Lukin, Oleg; Schubert, Dirk; Müller, Claudia M; Schweizer, W Bernd; Gramlich, Volker; Schneider, Julian; Dolgonos, Grygoriy; Shivanyuk, Alexander

    2009-07-01

    A detailed single-crystal X-ray study of conformationally flexible sulfonimide-based dendritic molecules with systematically varied molecular architectures was undertaken. Thirteen crystal structures reported in this work include 9 structures of the second-generation dendritic sulfonimides decorated with different aryl groups, 2 compounds bearing branches of both second and first generation, and 2 representatives of the first generation. Analysis of the packing patterns of 9 compounds bearing second-generation branches shows that despite their lack of strong directive functional groups there is a repeatedly reproduced intermolecular interaction mode consisting in an anchor-type packing of complementary second-generation branches of neighbouring molecules. The observed interaction tolerates a wide range of substituents in meta- and para-positions of the peripheral arylsulfonyl rings. Quantum chemical calculations of the molecule-molecule interaction energies agree at the qualitative level with the packing preferences found in the crystalline state. The calculations can therefore be used as a tool to rationalize and predict molecular structures with commensurate and non-commensurate branches for programming of different packing modes in crystal. PMID:19549870

  16. Engineering crystals of dendritic molecules

    PubMed Central

    Lukin, Oleg; Schubert, Dirk; Müller, Claudia M.; Schweizer, W. Bernd; Gramlich, Volker; Schneider, Julian; Dolgonos, Grygoriy; Shivanyuk, Alexander

    2009-01-01

    A detailed single-crystal X-ray study of conformationally flexible sulfonimide-based dendritic molecules with systematically varied molecular architectures was undertaken. Thirteen crystal structures reported in this work include 9 structures of the second-generation dendritic sulfonimides decorated with different aryl groups, 2 compounds bearing branches of both second and first generation, and 2 representatives of the first generation. Analysis of the packing patterns of 9 compounds bearing second-generation branches shows that despite their lack of strong directive functional groups there is a repeatedly reproduced intermolecular interaction mode consisting in an anchor-type packing of complementary second-generation branches of neighbouring molecules. The observed interaction tolerates a wide range of substituents in meta- and para-positions of the peripheral arylsulfonyl rings. Quantum chemical calculations of the molecule-molecule interaction energies agree at the qualitative level with the packing preferences found in the crystalline state. The calculations can therefore be used as a tool to rationalize and predict molecular structures with commensurate and non-commensurate branches for programming of different packing modes in crystal. PMID:19549870

  17. Final Report: Cooling Molecules with Laser Light

    SciTech Connect

    Di Rosa, Michael D.

    2012-05-08

    Certain diatomic molecules are disposed to laser cooling in the way successfully applied to certain atoms and that ushered in a revolution in ultracold atomic physics, an identification first made at Los Alamos and which took root during this program. Despite their manipulation into numerous achievements, atoms are nonetheless mundane denizens of the quantum world. Molecules, on the other hand, with their internal degrees of freedom and rich dynamical interplay, provide considerably more complexity. Two main goals of this program were to demonstrate the feasibility of laser-cooling molecules to the same temperatures as laser-cooled atoms and introduce a means for collecting laser-cooled molecules into dense ensembles, a foundational start of studies and applications of ultracold matter without equivalence in atomic systems.

  18. Enzymatic DNA molecules

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor); Breaker, Ronald R. (Inventor)

    1998-01-01

    The present invention discloses deoxyribonucleic acid enzymes--catalytic or enzymatic DNA molecules--capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.

  19. Adhesion molecules and receptors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adhesion molecules are necessary for leukocyte trafficking and differentiation. They serve to initiate cell-cell interactions under conditions of shear, and they sustain the cell-cell and cell-matrix interactions needed for cellular locomotion. They also can serve directly as signaling molecules act...

  20. Molecules between the Stars.

    ERIC Educational Resources Information Center

    Verschuur, Gerrit L.

    1987-01-01

    Provides a listing of molecules discovered to date in the vast interstellar clouds of dust and gas. Emphasizes the recent discoveries of organic molecules. Discusses molecular spectral lines, MASERs (microwave amplification by stimulated emission of radiation), molecular clouds, and star birth. (TW)

  1. Parallel Molecular Dynamics Program for Molecules

    Energy Science and Technology Software Center (ESTSC)

    1995-03-07

    ParBond is a parallel classical molecular dynamics code that models bonded molecular systems, typically of an organic nature. It uses classical force fields for both non-bonded Coulombic and Van der Waals interactions and for 2-, 3-, and 4-body bonded (bond, angle, dihedral, and improper) interactions. It integrates Newton''s equation of motion for the molecular system and evaluates various thermodynamical properties of the system as it progresses.

  2. Chemical Recycling of Molecules in Cometary Comae

    NASA Astrophysics Data System (ADS)

    Boice, Daniel C.; Kawakita, Hideyo; Shinnaka, Yoshiharu; Kobayashi, Hitomi

    2015-08-01

    Modeling is essential to understand the important physical and chemical processes that occur in cometary comae, especially the relationship between native and sibling molecules, such as, HCN and CN. Photochemistry is a major source of ions and electrons that further initiate key gas-phase reactions, leading to the plethora of molecules and atoms observed in comets. The effects of photoelectrons that react via impacts are important to the overall ionization in the inner coma. We have found that many molecules undergo protonation reactions with primarily water, followed by electron recombination resulting in the original molecules in a vibrationally excited state. These excited molecules spontaneously emit photons back to the ground state. We identify this series of reactions as chemical “recycling.” We discuss the importance of this mechanism for HCN, NH3, and water in comets. We also identify other relevant processes in the collision-dominated, inner coma of a comet within a global modeling framework to better understand observations and in situ measurements of cometary species, especially relationships between native and sibling molecules for the Rosetta Mission to Comet 67P/Churyumov-Gerasimenko.Acknowledgements: We appreciate support from the NSF Planetary Astronomy Program under Grant No. 0908529. This program is partially supported by the MEXT Supported Program for the Strategic Research Foundation at Private Universities, 2014-2018.

  3. Ultracold polar KRb molecules

    NASA Astrophysics Data System (ADS)

    Neyenhuis, Brian; Chotia, Amodsen; Moses, Steven; Ye, Jun; Jin, Deborah

    2011-05-01

    Ultracold polar molecules in the quantum degenerate regime open the possibility of realizing quantum gases with long-range, and spatially anisotropic, interparticle interactions. Currently, we can create a gas of ultracold fermionic ground-state KRb molecules in with a peak density of 1012 cm-3 and a temperature just 1.4 times the Fermi temperature. We will report on efforts to further cool this gas of molecules. One possibility is to evaporatively cool a spin-polarized molecular Fermi gas confined in quasi-2D, where we would rely on dipole-dipole interactions for rethermalization. We acknowledge funding from NIST, NSF, and AFOSR-MURI.

  4. Poisson's spot with molecules

    SciTech Connect

    Reisinger, Thomas; Holst, Bodil; Patel, Amil A.; Smith, Henry I.; Reingruber, Herbert; Fladischer, Katrin; Ernst, Wolfgang E.; Bracco, Gianangelo

    2009-05-15

    In the Poisson-spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. In this paper we report the observation of Poisson's spot using a beam of neutral deuterium molecules. The wavelength independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson's spot a promising candidate for applications ranging from the study of large molecule diffraction to patterning with molecules.

  5. Poisson's spot with molecules

    NASA Astrophysics Data System (ADS)

    Reisinger, Thomas; Patel, Amil A.; Reingruber, Herbert; Fladischer, Katrin; Ernst, Wolfgang E.; Bracco, Gianangelo; Smith, Henry I.; Holst, Bodil

    2009-05-01

    In the Poisson-spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. In this paper we report the observation of Poisson’s spot using a beam of neutral deuterium molecules. The wavelength independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson’s spot a promising candidate for applications ranging from the study of large molecule diffraction to patterning with molecules.

  6. Single-Molecule Enzymology

    SciTech Connect

    Xie, Xiaoliang; Lu, H PETER.

    1999-06-04

    Viewing a movie of an enzyme molecule made from molecular dynamics (MD) simulation, we see incredible details of molecular motions, be it a change of the conformation or the action of a chemical reaction.

  7. Of Molecules and Models.

    ERIC Educational Resources Information Center

    Brinner, Bonnie

    1992-01-01

    Presents an activity in which models help students visualize both the DNA process and transcription. After constructing DNA, RNA messenger, and RNA transfer molecules; students model cells, protein synthesis, codons, and RNA movement. (MDH)

  8. Polyatomic molecule vibrations

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Polyatomic molecule vibrations are analyzed as harmonic vibrations along normal coordinates. The energy eigenvalues are found for linear and nonlinear symmetric triatomic molecules for valence bond models of the potential function with arbitrary coupling coefficients; such models can usually be fitted to observed energy levels with reasonably good accuracy. Approximate normal coordinates for the H2O molecule are discussed. Degenerate vibrational modes such as occur in CO2 are analyzed and expressions for Fermi resonance between close-lying states of the same symmetry are developed. The bending modes of linear triatomic molecules are expressed in terms of Laguerre polynomials in cylindrical coordinates as well as in terms of Hermite polynomials in Cartesian coordinates. The effects of large-amplitude bending such as occur in the C3 molecule are analyzed, along with anharmonic effects, which split the usually degenerate bending mode energy levels. Finally, the vibrational frequencies, degeneracies, and symmetry properties of XY3, X2Y2, and XY4 type molecules are discussed.

  9. Positron binding to molecules

    NASA Astrophysics Data System (ADS)

    Danielson, J. R.

    2011-05-01

    While there is theoretical evidence that positrons can bind to atoms, calculations for molecules are much less precise. Unfortunately, there have been no measurements of positron-atom binding, due primarily to the difficulty in forming positron-atom bound states in two-body collisions. In contrast, positrons attach to molecules via Feshbach resonances (VFR) in which a vibrational mode absorbs the excess energy. Using a high-resolution positron beam, this VFR process has been studied to measure binding energies for more than 40 molecules. New measurements will be described in two areas: positron binding to relatively simple molecules, for which theoretical calculations appear to be possible; and positron binding to molecules with large permanent dipole moments, which can be compared to analogous, weakly bound electron-molecule (negative-ion) states. Binding energies range from 75 meV for CS2 (no dipole moment) to 180 meV for acetonitrile (CH3CN). Other species studied include aldehydes and ketones, which have permanent dipole moments in the range 2.5 - 3.0 debye. The measured binding energies are surprisingly large (by a factor of 10 to 100) compared to those for the analogous negative ions, and these differences will be discussed. New theoretical calculations for positron-molecule binding are in progress, and a recent result for acetonitrile will be discussed. This ability to compare theory and experiment represents a significant step in attempts to understand positron binding to matter. In collaboration with A. C. L. Jones, J. J. Gosselin, and C. M. Surko, and supported by NSF grant PHY 07-55809.

  10. Understanding ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Julienne, Paul

    2009-05-01

    The successful production of a dense sample of ultracold ground state KRb polar molecules [1] opens the door to a new era of research with dipolar gases and lattices of such species. This feat was achieved by first associating a K and a Rb atom to make a weakly bound Feshbach molecule and then coherently transferring the population to the ground vibrational level of the molecule. This talk focuses on theoretical issues associated with making and using ultracold polar molecules, using KRb as an example [2]. Full understanding of this species and the processes by which it is made requires taking advantage of accurate molecular potentials [3], ab initio calculations [4], and the properties of the long-range potential. A highly accurate model is available for KRb for all bound states below the ground state separated atom limit and could be constructed for other species. The next step is to develop an understanding of the interactions between polar molecules, and their control in the ultracold domain. Understanding long-range interactions and threshold resonances will be crucial for future work. [1] K.-K. Ni, et al, Science 322, 231(2008). [2] P. S. Julienne, arXiv:0812:1233. [3] Pashov et al., Phys. Rev. A76, 022511 (2007). [4] S. Kotochigova, et al., arXiv:0901.1486.

  11. Molecules on ice

    SciTech Connect

    Clary, D.C.

    1996-03-15

    The ozone hole that forms in the spring months over the Antarctic is thought to be produced through a network of chemical reactions catalyzed by the surfaces of ice crystals in polar stratospheric clouds (PSCs). A reaction between chlorine reservoir molecules, such as HCl + ClONO{sub 2} > HNO{sub 3} + Cl{sub 2}, is kinetically forbidden in the gas phase but proceeds quickly on the surface of ice and produces Cl{sub 2} molecules that are photodissociated by sunlight to yield the Cl atoms that destroy ozone. This destructive chain of events begins when HCl molecules stick to the ice crystals, and the mechanism for this crucial sticking process has been the subject of much debate. Recent work describes a mechanism that explains how HCl sticks to ice. This article goes on to detail research focusing surface reactions in stratospheric chemistry. 9 refs., 1 fig.

  12. Positronium ions and molecules

    NASA Technical Reports Server (NTRS)

    Ho, Y. K.

    1990-01-01

    Recent theoretical studies on positronium ions and molecules are discussed. A positronium ion is a three particle system consisting of two electrons in singlet spin state, and a positron. Recent studies include calculations of its binding energy, positron annihilation rate, and investigations of its doubly excited resonant states. A positronium molecule is a four body system consisting of two positrons and two electrons in an overall singlet spin state. The recent calculations of its binding energy against the dissociation into two positronium atoms, and studies of auto-detaching states in positronium molecules are discussed. These auto-dissociating states, which are believed to be part of the Rydberg series as a result of a positron attaching to a negatively charged positronium ion, Ps-, would appear as resonances in Ps-Ps scattering.

  13. Atomic branching in molecules

    NASA Astrophysics Data System (ADS)

    Estrada, Ernesto; Rodríguez-Velázquez, Juan A.; Randić, Milan

    A graph theoretic measure of extended atomic branching is defined that accounts for the effects of all atoms in the molecule, giving higher weight to the nearest neighbors. It is based on the counting of all substructures in which an atom takes part in a molecule. We prove a theorem that permits the exact calculation of this measure based on the eigenvalues and eigenvectors of the adjacency matrix of the graph representing a molecule. The definition of this measure within the context of the Hückel molecular orbital (HMO) and its calculation for benzenoid hydrocarbons are also studied. We show that the extended atomic branching can be defined using any real symmetric matrix, as well as any Hermitian (self-adjoint) matrix, which permits its calculation in topological, geometrical, and quantum chemical contexts.

  14. Single-Molecule Bioelectronics

    PubMed Central

    Rosenstein, Jacob K.; Lemay, Serge G.; Shepard, Kenneth L.

    2014-01-01

    Experimental techniques which interface single biomolecules directly with microelectronic systems are increasingly being used in a wide range of powerful applications, from fundamental studies of biomolecules to ultra-sensitive assays. Here we review several technologies which can perform electronic measurements of single molecules in solution: ion channels, nanopore sensors, carbon nanotube field-effect transistors, electron tunneling gaps, and redox cycling. We discuss the shared features among these techniques that enable them to resolve individual molecules, and discuss their limitations. Recordings from each of these methods all rely on similar electronic instrumentation, and we discuss the relevant circuit implementations and potential for scaling these single-molecule bioelectronic interfaces to high-throughput arrayed sensing platforms. PMID:25529538

  15. Single-molecule bioelectronics.

    PubMed

    Rosenstein, Jacob K; Lemay, Serge G; Shepard, Kenneth L

    2015-01-01

    Experimental techniques that interface single biomolecules directly with microelectronic systems are increasingly being used in a wide range of powerful applications, from fundamental studies of biomolecules to ultra-sensitive assays. In this study, we review several technologies that can perform electronic measurements of single molecules in solution: ion channels, nanopore sensors, carbon nanotube field-effect transistors, electron tunneling gaps, and redox cycling. We discuss the shared features among these techniques that enable them to resolve individual molecules, and discuss their limitations. Recordings from each of these methods all rely on similar electronic instrumentation, and we discuss the relevant circuit implementations and potential for scaling these single-molecule bioelectronic interfaces to high-throughput arrayed sensing platforms. PMID:25529538

  16. Photochemistry of interstellar molecules

    NASA Technical Reports Server (NTRS)

    Stief, L. J.

    1971-01-01

    The photochemistry of two diatomic and eight polyatomic molecules is discussed quantitatively. For an interstellar molecule, the lifetime against photodecomposition depends upon the absorption cross section, the quantum yield or probability of dissociation following photon absorption, and the interstellar radiation field. The constant energy density of Habing is used for the unobserved regions of interstellar radiation field, and the field in obscuring clouds is estimated by combining the constant flux with the observed interstellar extinction curve covering the visible and ultraviolet regions. Lifetimes against photodecomposition in the unobscured regions and as a function of increasing optical thickness in obscuring clouds are calculated for the ten species. The results show that, except for CO, all the molecules have comparable lifetimes of less than one hundred years. Thus they can exist only in dense clouds and can never have been exposed to the unobscured radiation. The calculations further show that the lifetimes in clouds of moderate opacity are of the order of one million years.

  17. Molecules in η Carinae

    NASA Astrophysics Data System (ADS)

    Loinard, Laurent; Menten, Karl M.; Güsten, Rolf; Zapata, Luis A.; Rodríguez, Luis F.

    2012-04-01

    We report the detection toward η Carinae of six new molecules, CO, CN, HCO+, HCN, HNC, and N2H+, and of two of their less abundant isotopic counterparts, 13CO and H13CN. The line profiles are moderately broad (~100 km s-1), indicating that the emission originates in the dense, possibly clumpy, central arcsecond of the Homunculus Nebula. Contrary to previous claims, CO and HCO+ do not appear to be underabundant in η Carinae. On the other hand, molecules containing nitrogen or the 13C isotope of carbon are overabundant by about one order of magnitude. This demonstrates that, together with the dust responsible for the dimming of η Carinae following the Great Eruption, the molecules detected here must have formed in situ out of CNO-processed stellar material.

  18. Poisson's Spot with Molecules

    NASA Astrophysics Data System (ADS)

    Reisinger, Thomas; Patel, Amil; Reingruber, Herbert; Fladischer, Katrin; Ernst, Wolfgang E.; Bracco, Gianangelo; Smith, Henry I.; Holst, Bodil

    2009-03-01

    In the Poisson-Spot experiment, waves emanating from a source are blocked by a circular obstacle. Due to their positive on-axis interference an image of the source (the Poisson spot) is observed within the geometrical shadow of the obstacle. The Poisson spot is the last of the classical optics experiments to be realized with neutral matter waves. In this paper we report the observation of Poisson's Spot using a beam of neutral deuterium molecules. The wavelength-independence and the weak constraints on angular alignment and position of the circular obstacle make Poisson's spot a promising candidate for applications ranging from the study of large-molecule diffraction and coherence in atom-lasers to patterning with large molecules.

  19. MOLECULES IN {eta} CARINAE

    SciTech Connect

    Loinard, Laurent; Menten, Karl M.; Guesten, Rolf; Zapata, Luis A.; Rodriguez, Luis F.

    2012-04-10

    We report the detection toward {eta} Carinae of six new molecules, CO, CN, HCO{sup +}, HCN, HNC, and N{sub 2}H{sup +}, and of two of their less abundant isotopic counterparts, {sup 13}CO and H{sup 13}CN. The line profiles are moderately broad ({approx}100 km s{sup -1}), indicating that the emission originates in the dense, possibly clumpy, central arcsecond of the Homunculus Nebula. Contrary to previous claims, CO and HCO{sup +} do not appear to be underabundant in {eta} Carinae. On the other hand, molecules containing nitrogen or the {sup 13}C isotope of carbon are overabundant by about one order of magnitude. This demonstrates that, together with the dust responsible for the dimming of {eta} Carinae following the Great Eruption, the molecules detected here must have formed in situ out of CNO-processed stellar material.

  20. Towards single molecule switches.

    PubMed

    Zhang, Jia Lin; Zhong, Jian Qiang; Lin, Jia Dan; Hu, Wen Ping; Wu, Kai; Xu, Guo Qin; Wee, Andrew T S; Chen, Wei

    2015-05-21

    The concept of using single molecules as key building blocks for logic gates, diodes and transistors to perform basic functions of digital electronic devices at the molecular scale has been explored over the past decades. However, in addition to mimicking the basic functions of current silicon devices, molecules often possess unique properties that have no parallel in conventional materials and promise new hybrid devices with novel functions that cannot be achieved with equivalent solid-state devices. The most appealing example is the molecular switch. Over the past decade, molecular switches on surfaces have been intensely investigated. A variety of external stimuli such as light, electric field, temperature, tunneling electrons and even chemical stimulus have been used to activate these molecular switches between bistable or even multiple states by manipulating molecular conformations, dipole orientations, spin states, charge states and even chemical bond formation. The switching event can occur either on surfaces or in break junctions. The aim of this review is to highlight recent advances in molecular switches triggered by various external stimuli, as investigated by low-temperature scanning tunneling microscopy (LT-STM) and the break junction technique. We begin by presenting the molecular switches triggered by various external stimuli that do not provide single molecule selectivity, referred to as non-selective switching. Special focus is then given to selective single molecule switching realized using the LT-STM tip on surfaces. Single molecule switches operated by different mechanisms are reviewed and discussed. Finally, molecular switches embedded in self-assembled monolayers (SAMs) and single molecule junctions are addressed. PMID:25757483

  1. Plasmonic nanostructures: artificial molecules.

    PubMed

    Wang, Hui; Brandl, Daniel W; Nordlander, Peter; Halas, Naomi J

    2007-01-01

    This Account describes a new paradigm for the relationship between the geometry of metallic nanostructures and their optical properties. While the interaction of light with metallic nanoparticles is determined by their collective electronic or plasmon response, a compelling analogy exists between plasmon resonances of metallic nanoparticles and wave functions of simple atoms and molecules. Based on this insight, an entire family of plasmonic nanostructures, artificial molecules, has been developed whose optical properties can be understood within this picture: nanoparticles (nanoshells, nanoeggs, nanomatryushkas, nanorice), multi-nanoparticle assemblies (dimers, trimers, quadrumers), and a nanoparticle-over-metallic film, an electromagnetic analog of the spinless Anderson model. PMID:17226945

  2. Prebiologically Important Interstellar Molecules

    NASA Astrophysics Data System (ADS)

    Kuan, Y.-J.; Huang, H.-C.; Charnley, S. B.; Tseng, W.-L.; Snyder, L. E.; Ehrenfreund, P.; Kisiel, Z.; Thorwirth, S.; Bohn, R. K.; Wilson, T. L.

    2004-06-01

    Understanding the organic chemistry of molecular clouds, particularly the formation of biologically important molecules, is fundamental to the study of the processes which lead to the origin, evolution and distribution of life in the Galaxy. Determining the level of molecular complexity attainable in the clouds, and the nature of the complex organic material available to protostellar disks and the planetary systems that form from them, requires an understanding of the possible chemical pathways and is therefore a central question in astrochemistry. We have thus searched for prebiologically important molecules in the hot molecular cloud cores: Sgr B2(N-LMH), W51 e1/e2 and Orion-KL. Among the molecules searched: Pyrimidine is the unsubstituted ring analogue for three of the DNA and RNA bases. 2H-Azirine and Aziridine are azaheterocyclic compounds. And Glycine is the simplest amino acid. Detections of these interstellar organic molecular species will thus have important implications for Astrobiology. Our preliminary results indicate a tentative detection of interstellar glycine. If confirmed, this will be the first detection of an amino acid in interstellar space and will greatly strengthen the thesis that interstellar organic molecules could have played a pivotal role in the prebiotic chemistry of the early Earth.

  3. Algebraic theory of molecules

    NASA Technical Reports Server (NTRS)

    Iachello, Franco

    1995-01-01

    An algebraic formulation of quantum mechanics is presented. In this formulation, operators of interest are expanded onto elements of an algebra, G. For bound state problems in nu dimensions the algebra G is taken to be U(nu + 1). Applications to the structure of molecules are presented.

  4. Mighty Molecule Models

    ERIC Educational Resources Information Center

    Brown, Tom; Rushton, Greg; Bencomo, Marie

    2008-01-01

    As part of the SMATHematics Project: The Wonder of Science, The Power of Mathematics--a collaborative partnership between Kennesaw State University and two local school districts, fifth graders had the opportunity to puzzle out chemical formulas of propane, methanol, and other important molecules. In addition, they explored properties that…

  5. Diversity in Biological Molecules

    ERIC Educational Resources Information Center

    Newbury, H. John

    2010-01-01

    One of the striking characteristics of fundamental biological processes, such as genetic inheritance, development and primary metabolism, is the limited amount of variation in the molecules involved. Natural selective pressures act strongly on these core processes and individuals carrying mutations and producing slightly sub-optimal versions of…

  6. The Science of Molecules

    ERIC Educational Resources Information Center

    Flory, Paul J.

    1974-01-01

    The author maintains that chemistry has a key role as the science of molecules and rejects the concept of chemistry as a branch of physics. The scope of chemistry, the philosophies underlying its practice, and the teaching of the subject also are discussed. (DT)

  7. OMG: Open Molecule Generator

    PubMed Central

    2012-01-01

    Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck. PMID:22985496

  8. OMG: Open Molecule Generator.

    PubMed

    Peironcely, Julio E; Rojas-Chertó, Miguel; Fichera, Davide; Reijmers, Theo; Coulier, Leon; Faulon, Jean-Loup; Hankemeier, Thomas

    2012-01-01

    Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck. PMID:22985496

  9. Building Diatomic and Triatomic Superatom Molecules.

    PubMed

    Champsaur, Anouck M; Velian, Alexandra; Paley, Daniel W; Choi, Bonnie; Roy, Xavier; Steigerwald, Michael L; Nuckolls, Colin

    2016-08-10

    In this study, we have developed a method to create Co6Se8 superatoms in which we program the metal-ligand bonds. We exclusively form the Co6Se8 core under simple reaction conditions with a facile separation of products that contain differential substitution of the core. The combination of Co2(CO)8 and PR3 with excess Se gives the differentially and directionally substituted superatoms, Co6Se8(CO)x(PR3)(6-x). The CO groups on the superatom can be exchanged quantitatively with phosphines and isonitriles. Substitution of the CO allows us to manipulate the type and length of chemical bridge between two redox-active superatomic centers in order to modulate intersuperatomic coupling. Linking two superatoms together allows us to form the simplest superatom molecule: a diatomic molecule. We extend the superatom molecule concept to link three superatoms together in a linear arrangement to form acyclic triatomic molecules. These superatom molecules have a rich electrochemical profile and chart a clear path to a whole family of superatom molecules with new and unusual collective properties. PMID:27410225

  10. Bacterial invasion reconstructed molecule by molecule

    SciTech Connect

    Werner, James H

    2009-01-01

    We propose to visualize the initial stages of bacterial infection of a human host cell with unmatched spatial and temporal resolution. This work will develop a new capability for the laboratory (super-resolution optical imaging), will test unresolved scientific hypotheses regarding host-pathogen interaction dynamics, and leverages state of the art 3D molecular tracking instrumentation developed recently by our group. There is much to be gained by applying new single molecule tools to the important and familiar problem of pathogen entry into a host cell. For example, conventional fluorescence microscopy has identified key host receptors, such as CD44 and {alpha}5{beta}1 integrin, that aggregate near the site of Salmonella typhimurium infection of human cells. However, due to the small size of the bacteria ({approx} 2 {micro}m) and the diffraction of the emitted light, one just sees a fluorescent 'blob' of host receptors that aggregate at the site of attachment, making it difficult to determine the exact number of receptors present or whether there is any particular spatial arrangement of the receptors that facilitates bacterial adhesion/entry. Using newly developed single molecule based super-resolution imaging methods, we will visualize how host receptors are directed to the site of pathogen adhesion and whether host receptors adopt a specific spatial arrangement for successful infection. Furthermore, we will employ our 3D molecular tracking methods to follow the injection of virulence proteins, or effectors, into the host cell by the pathogen Type III secretion system (TTSS). We expect these studies to provide mechanistic insights into the early events of pathogen infection that have here-to-fore been technically beyond our reach. Our Research Goals are: Goal 1--Construct a super-resolution fluorescence microscope and use this new capability to image the spatial distribution of different host receptors (e.g. CD44, as {alpha}5{beta}1 integrin) at the point of

  11. A toy model for a diatomic molecule

    NASA Astrophysics Data System (ADS)

    Hecker Denschlag, Johannes

    2016-08-01

    We introduce a toy model for a diatomic molecule which is based on coupling electronic and nuclear spins to a rigid rotor. Despite its simplicity, the model can be used scientifically to analyze and understand complex molecular hyperfine spectra. In addition, the model has educational value as a number of fundamental symmetries and conservation laws of the molecule can be studied. Because of its simple structure, the model can be readily implemented as a computer program with comparatively short computing times on the order of a few seconds.

  12. Computer Modelling of Biological Molecules: Free Resources on the Internet.

    ERIC Educational Resources Information Center

    Millar, Neil

    1996-01-01

    Describes a three-dimensional computer modeling system for biological molecules which is suitable for sixth-form teaching. Consists of the modeling program "RasMol" together with structure files of proteins, DNA, and small biological molecules. Describes how the whole system can be downloaded from various sites on the Internet. (Author/JRH)

  13. Single-molecule electrophoresis

    SciTech Connect

    Castro, A.; Shera, E.B.

    1995-09-15

    A novel method for the detection and identification of single molecules in solution has been devised, computer simulated, and experimentally achieved. The technique involves the determination of electrophoretic velocities by measuring the time required for individual molecules to travel a fixed distance between two laser beams. Computer simulations of the process were performed before-hand in order to estimate the experimental feasibility of the method and to determine the optimum values for the various experimental parameters. Examples of the use of the technique for the ultrasensitive detection and identification of rhodamine-6G, a mixture of DNA restriction fragments, and a mixture of proteins in aqueous solution are presented. 20 refs., 8 figs.

  14. Strange skyrmion molecules

    NASA Astrophysics Data System (ADS)

    Kopeliovich, Vladimir B.; Stern, Boris E.

    1997-05-01

    Composed skyrmions with B=2, strangeness content close to 0.5 and the binding energy of several tens of Mev are described. These skyrmions are obtained starting from the system of two B=1 hedgehogs located in different SU(2) subgroups of SU(3) and have the mass and baryon number distribution of molecular (dipole) type. The quantization of zero modes of skyrmion molecules and physics consequences of their existence are discussed.

  15. Strange skyrmion molecules

    SciTech Connect

    Kopeliovich, Vladimir B.; Stern, Boris E.

    1997-05-20

    Composed skyrmions with B=2, strangeness content close to 0.5 and the binding energy of several tens of Mev are described. These skyrmions are obtained starting from the system of two B=1 hedgehogs located in different SU(2) subgroups of SU(3) and have the mass and baryon number distribution of molecular (dipole) type. The quantization of zero modes of skyrmion molecules and physics consequences of their existence are discussed.

  16. Single Molecule Mechanochemistry

    NASA Astrophysics Data System (ADS)

    Li, Shaowei; Zhang, Yanxing; Ho, Wilson; Wu, Ruqian; Ruqian Wu, Yanxing Zhang Team; Wilson Ho, Shaowei Li Team

    Mechanical forces can be used to trigger chemical reactions through bending and stretching of chemical bonds. Using the reciprocating movement of the tip of a scanning tunneling microscope (STM), mechanical energy can be provided to a single molecule sandwiched between the tip and substrate. When the mechanical pulse center was moved to the outer ring feature of a CO molecule, the reaction rate was significantly increased compared with bare Cu surface and over Au atoms. First, DFT calculations show that the presence of CO makes the Cu cavity more attractive toward H2 Second, H2 prefers the horizontal adsorption geometry in the Cu-Cu and Au-Cu cavities and no hybridization occurs between the antibonding states of H2 and states of Cu atoms. While H2 loses electrons from its bonding state in all three cavities, the filling of its anti-bonding state only occurs in the CO-Cu cavity. Both make the CO-Cu cavity much more effectively to chop the H2 molecule. Work was supported by the National Science Foundation Center for Chemical Innovation on Chemistry at the Space-Time Limit (CaSTL) under Grant No. CHE-1414466.

  17. Model molecules mimicking asphaltenes.

    PubMed

    Sjöblom, Johan; Simon, Sébastien; Xu, Zhenghe

    2015-04-01

    Asphalthenes are typically defined as the fraction of petroleum insoluble in n-alkanes (typically heptane, but also hexane or pentane) but soluble in toluene. This fraction causes problems of emulsion formation and deposition/precipitation during crude oil production, processing and transport. From the definition it follows that asphaltenes are not a homogeneous fraction but is composed of molecules polydisperse in molecular weight, structure and functionalities. Their complexity makes the understanding of their properties difficult. Proper model molecules with well-defined structures which can resemble the properties of real asphaltenes can help to improve this understanding. Over the last ten years different research groups have proposed different asphaltene model molecules and studied them to determine how well they can mimic the properties of asphaltenes and determine the mechanisms behind the properties of asphaltenes. This article reviews the properties of the different classes of model compounds proposed and present their properties by comparison with fractionated asphaltenes. After presenting the interest of developing model asphaltenes, the composition and properties of asphaltenes are presented, followed by the presentation of approaches and accomplishments of different schools working on asphaltene model compounds. The presentation of bulk and interfacial properties of perylene-based model asphaltene compounds developed by Sjöblom et al. is the subject of the next part. Finally the emulsion-stabilization properties of fractionated asphaltenes and model asphaltene compounds is presented and discussed. PMID:25638443

  18. Photonic Molecule Lasers Revisited

    NASA Astrophysics Data System (ADS)

    Gagnon, Denis; Dumont, Joey; Déziel, Jean-Luc; Dubé, Louis J.

    2014-05-01

    Photonic molecules (PMs) formed by coupling two or more optical resonators are ideal candidates for the fabrication of integrated microlasers, photonic molecule lasers. Whereas most calculations on PM lasers have been based on cold-cavity (passive) modes, i.e. quasi-bound states, a recently formulated steady-state ab initio laser theory (SALT) offers the possibility to take into account the spectral properties of the underlying gain transition, its position and linewidth, as well as incorporating an arbitrary pump profile. We will combine two theoretical approaches to characterize the lasing properties of PM lasers: for two-dimensional systems, the generalized Lorenz-Mie theory will obtain the resonant modes of the coupled molecules in an active medium described by SALT. Not only is then the theoretical description more complete, the use of an active medium provides additional parameters to control, engineer and harness the lasing properties of PM lasers for ultra-low threshold and directional single-mode emission. We will extend our recent study and present new results for a number of promising geometries. The authors acknowledge financial support from NSERC (Canada) and the CERC in Photonic Innovations of Y. Messaddeq.

  19. Molecules in interstellar clouds

    NASA Astrophysics Data System (ADS)

    Irvine, W. M.; Hjalmarson, A.; Rydbeck, O. E. H.

    The physical conditions and chemical compositions of the gas in interstellar clouds are reviewed in light of the importance of interstellar clouds for star formation and the origin of life. The Orion A region is discussed as an example of a giant molecular cloud where massive stars are being formed, and it is pointed out that conditions in the core of the cloud, with a kinetic temperature of about 75 K and a density of 100,000-1,000,000 molecules/cu cm, may support gas phase ion-molecule chemistry. The Taurus Molecular Clouds are then considered as examples of cold, dark, relatively dense interstellar clouds which may be the birthplaces of solar-type stars and which have been found to contain the heaviest interstellar molecules yet discovered. The molecular species identified in each of these regions are tabulated, including such building blocks of biological monomers as H2O, NH3, H2CO, CO, H2S, CH3CN and H2, and more complex species such as HCOOCH3 and CH3CH2CN.

  20. Epithelial Cell Adhesion Molecule

    PubMed Central

    Trzpis, Monika; McLaughlin, Pamela M.J.; de Leij, Lou M.F.H.; Harmsen, Martin C.

    2007-01-01

    The epithelial cell adhesion molecule (EpCAM, CD326) is a glycoprotein of ∼40 kd that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. Normal epithelia express EpCAM at a variable but generally lower level than carcinoma cells. In early studies, EpCAM was proposed to be a cell-cell adhesion molecule. However, recent insights revealed a more versatile role for EpCAM that is not limited only to cell adhesion but includes diverse processes such as signaling, cell migration, proliferation, and differentiation. Cell surface expression of EpCAM may actually prevent cell-cell adhesion. Here, we provide a comprehensive review of the current knowledge on EpCAM biology in relation to other cell adhesion molecules. We discuss the implications of the newly identified functions of EpCAM in view of its prognostic relevance in carcinoma, inflammatory pathophysiology, and tissue development and regeneration as well as its role in normal epithelial homeostasis. PMID:17600130

  1. Calculating Henry’s Constants of Charged Molecules Using SPARC

    EPA Science Inventory

    SPARC Performs Automated Reasoning in Chemistry is a computer program designed to model physical and chemical properties of molecules solely based on thier chemical structure. SPARC uses a toolbox of mechanistic perturbation models to model intermolecular interactions. SPARC has ...

  2. ION AND MOLECULE SENSORS USING MOLECULAR RECOGNITION IN LUMINESCENT, CONDUCTIVE POLYMERS

    EPA Science Inventory

    This program integrates three individual, highly interactive projects that will use molecular recognition strategies to develop sensor technology based on luminescent, conductive polymers that contain sites for binding specific molecules or ions in the presence of related molecul...

  3. Negative ions of polyatomic molecules.

    PubMed Central

    Christophorou, L G

    1980-01-01

    In this paper general concepts relating to, and recent advances in, the study of negative ions of polyatomic molecules area discussed with emphasis on halocarbons. The topics dealt with in the paper are as follows: basic electron attachment processes, modes of electron capture by molecules, short-lived transient negative ions, dissociative electron attachment to ground-state molecules and to "hot" molecules (effects of temperature on electron attachment), parent negative ions, effect of density, nature, and state of the medium on electron attachment, electron attachment to electronically excited molecules, the binding of attached electrons to molecules ("electron affinity"), and the basic and the applied significance of negative-ion studies. PMID:7428744

  4. Watching single molecules dance

    NASA Astrophysics Data System (ADS)

    Mehta, Amit Dinesh

    Molecular motors convert chemical energy, from ATP hydrolysis or ion flow, into mechanical motion. A variety of increasingly precise mechanical probes have been developed to monitor and perturb these motors at the single molecule level. Several outstanding questions can be best approached at the single molecule level. These include: how far does a motor progress per energy quanta consumed? how does its reaction cycle respond to load? how many productive catalytic cycles can it undergo per diffusional encounter with its track? and what is the mechanical stiffness of a single molecule connection? A dual beam optical trap, in conjunction with in vitro ensemble motility assays, has been used to characterize two members of the myosin superfamily: muscle myosin II and chick brain myosin V. Both move the helical polymer actin, but myosin II acts in large ensembles to drive muscle contraction or cytokinesis, while myosin V acts in small numbers to transport vesicles. An optical trapping apparatus was rendered sufficiently precise to identify a myosin working stroke with 1nm or so, barring systematic errors such as those perhaps due to random protein orientations. This and other light microscopic motility assays were used to characterize myosin V: unlike myosin II this vesicle transport protein moves through many increments of travel while remaining strongly bound to a single actin filament. The step size, stall force, and travel distance of myosin V reveal a remarkably efficient motor capable of moving along a helical track for over a micrometer without significantly spiraling around it. Such properties are fully consistent with the putative role of an organelle transport motor, present in small numbers to maintain movement over long ranges relative to cellular size scales. The contrast between myosin II and myosin V resembles that between a human running on the moon and one walking on earth, where the former allows for faster motion when in larger ensembles but for less

  5. Leucocyte cellular adhesion molecules.

    PubMed

    Yong, K; Khwaja, A

    1990-12-01

    Leucocytes express adhesion promoting receptors which mediate cell-cell and cell-matrix interactions. These adhesive interactions are crucial to the regulation of haemopoiesis and thymocyte maturation, the direction and control of leucocyte traffic and migration through tissues, and in the development of immune and non-immune inflammatory responses. Several families of adhesion receptors have been identified (Table). The leucocyte integrin family comprises 3 alpha beta heterodimeric membrane glycoproteins which share a common beta subunit, designated CD18. The alpha subunits of each of the 3 members, lymphocyte function associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1) and p150,95 are designated CD11a, b and c respectively. These adhesion molecules play a critical part in the immune and inflammatory responses of leucocytes. The leucocyte integrin family is, in turn, part of the integrin superfamily, members of which are evolutionally, structurally and functionally related. Another Integrin subfamily found on leucocytes is the VLA group, so-called because the 'very late activation antigens' VLA-1 and VLA-2 were originally found to appear late in T-cell activation. Members of this family function mainly as extracellular matrix adhesion receptors and are found both on haemopoietic and non-haemopoietic cells. They play a part in diverse cellular functions including tissue organisation, lymphocyte recirculation and T-cell immune responses. A third integrin subfamily, the cytoadhesins, are receptors on platelets and endothelial cells which bind extracellular matrix proteins. A second family of adhesion receptors is the immunoglobulin superfamily, members of which include CD2, LFA-3 and ICAM-1, which participate in T-cell adhesive interactions, and the antigen-specific receptors of T and B cells, CD4, CD8 and the MHC Class I and II molecules. A recently recognised family of adhesion receptors is the selectins, characterised by a common lectin domain. Leucocyte

  6. Single Molecule Transcription Elongation

    PubMed Central

    Galburt, Eric A.; Grill, Stephan W.; Bustamante, Carlos

    2009-01-01

    Single molecule optical trapping assays have now been applied to a great number of macromolecular systems including DNA, RNA, cargo motors, restriction enzymes, DNA helicases, chromosome remodelers, DNA polymerases and both viral and bacterial RNA polymerases. The advantages of the technique are the ability to observe dynamic, unsynchronized molecular processes, to determine the distributions of experimental quantities and to apply force to the system while monitoring the response over time. Here, we describe the application of these powerful techniques to study the dynamics of transcription elongation by RNA polymerase II from Saccharomyces cerevisiae. PMID:19426807

  7. Ultra-cold molecule production.

    SciTech Connect

    Ramirez-Serrano, Jamie; Chandler, David W.; Strecker, Kevin; Rahn, Larry A.

    2005-12-01

    The production of Ultra-cold molecules is a goal of many laboratories through out the world. Here we are pursuing a unique technique that utilizes the kinematics of atomic and molecular collisions to achieve the goal of producing substantial numbers of sub Kelvin molecules confined in a trap. Here a trap is defined as an apparatus that spatially localizes, in a known location in the laboratory, a sample of molecules whose temperature is below one degree absolute Kelvin. Further, the storage time for the molecules must be sufficient to measure and possibly further cool the molecules. We utilize a technique unique to Sandia to form cold molecules from near mass degenerate collisions between atoms and molecules. This report describes the progress we have made using this novel technique and the further progress towards trapping molecules we have cooled.

  8. Advancing Biological Understanding and Therapeutics Discovery with Small Molecule Probes

    PubMed Central

    Schreiber, Stuart L.; Kotz, Joanne D.; Li, Min; Aubé, Jeffrey; Austin, Christopher P.; Reed, John C.; Rosen, Hugh; White, E. Lucile; Sklar, Larry A.; Lindsley, Craig W.; Alexander, Benjamin R.; Bittker, Joshua A.; Clemons, Paul A.; de Souza, Andrea; Foley, Michael A.; Palmer, Michelle; Shamji, Alykhan F.; Wawer, Mathias J.; McManus, Owen; Wu, Meng; Zou, Beiyan; Yu, Haibo; Golden, Jennifer E.; Schoenen, Frank J.; Simeonov, Anton; Jadhav, Ajit; Jackson, Michael R.; Pinkerton, Anthony B.; Chung, Thomas D.Y.; Griffin, Patrick R.; Cravatt, Benjamin F.; Hodder, Peter S.; Roush, William R.; Roberts, Edward; Chung, Dong-Hoon; Jonsson, Colleen B.; Noah, James W.; Severson, William E.; Ananthan, Subramaniam; Edwards, Bruce; Oprea, Tudor I.; Conn, P. Jeffrey; Hopkins, Corey R.; Wood, Michael R.; Stauffer, Shaun R.; Emmitte, Kyle A.

    2015-01-01

    Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the U.S. National Institutes of Health launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines, but also highlight the need to innovate the science of therapeutic discovery. PMID:26046436

  9. Covalent Chemistry beyond Molecules.

    PubMed

    Jiang, Juncong; Zhao, Yingbo; Yaghi, Omar M

    2016-03-16

    Linking molecular building units by covalent bonds to make crystalline extended structures has given rise to metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), thus bringing the precision and versatility of covalent chemistry beyond discrete molecules to extended structures. The key advance in this regard has been the development of strategies to overcome the "crystallization problem", which is usually encountered when attempting to link molecular building units into covalent solids. Currently, numerous MOFs and COFs are made as crystalline materials in which the large size of the constituent units provides for open frameworks. The molecular units thus reticulated become part of a new environment where they have (a) lower degrees of freedom because they are fixed into position within the framework; (b) well-defined spatial arrangements where their properties are influenced by the intricacies of the pores; and (c) ordered patterns onto which functional groups can be covalently attached to produce chemical complexity. The notion of covalent chemistry beyond molecules is further strengthened by the fact that covalent reactions can be carried out on such frameworks, with full retention of their crystallinity and porosity. MOFs are exemplars of how this chemistry has led to porosity with designed metrics and functionality, chemically-rich sequences of information within their frameworks, and well-defined mesoscopic constructs in which nanoMOFs enclose inorganic nanocrystals and give them new levels of spatial definition, stability, and functionality. PMID:26863450

  10. Polymorphisms of co-inhibitory molecules (CTLA-4/PD-1/PD-L1) and the risk of non-small cell lung cancer in a Chinese population

    PubMed Central

    Ma, Yuan; Liu, Xiuchun; Zhu, Jingyan; Li, Wanhu; Guo, Liangjun; Han, Xiao; Song, Bao; Cheng, Sensen; Jie, Liu

    2015-01-01

    Lung cancer is a leading cause of cancer-related death in China, with non-small cell lung cancer (NSCLC) comprises the most common form. Co-inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1) and its ligand PD-L1, play a key roles in the physiopathological process of tumorigenesis. To investigate whether genetic variations of co-inhibitory molecules are associated with the risk of NSCLC, we analyzed polymorphisms of CTLA-4 (-318, +49), PD-1 (PD-1.1, PD-1.3, PD-1.5, PD-1.9) and PD-L1 (+8293) in a cohort of 528 NSCLC subjects and 600 healthy controls. By restriction fragment length polymorphism (RFLP) method, we found that the distributions of the CTLA-4 and PD-1 gene polymorphisms were similar between NSCLC patients and healthy controls. However, for the PD-L1 8923 A/C polymorphism, frequencies of the AC genotype and C-allele were significantly higher in NSCLC patients than in healthy controls (odds ratio [OR] =1.55; 95% confidence interval [CI] 1.13-2.13; P=0.006; OR=1.52; 95% CI 1.14-2.04; P=0.004, respectively). Stratification analysis revealed that prevalence of the 8923C allele was significantly increased in NSCLC patients who smoke compared to those non-smoking patients (OR=1.51; 95% CI 1.00-2.28; P<0.05). Moreover, NSCLC patients carrying the C-allele had higher risk of regional lymph node metastasis than those carrying the A-allele (OR=5.65; 95% CI 2.45~13.03; P<0.001). These data suggest that PD-L1+8293A>C polymorphism may play a role in the development and progression of NSCLC. PMID:26629188

  11. Molecules in the Spotlight

    SciTech Connect

    Cryan, James

    2010-01-26

    SLAC has just unveiled the world's first X-ray laser, the LCLS. This machine produces pulses of X-rays that are ten billion times brighter than those from conventional sources. One of the goals of this machine is to make movies of chemical reactions, including reactions necessary for life and reactions that might power new energy technologies. This public lecture will show the first results from the LCLS. As a first target, we have chosen nitrogen gas, the main component of the air we breathe. Using the unprecedented power of the LCLS X-rays as a blasting torch, we have created new forms of this molecule and with unique electronic arrangements. Please share with us the first insights from this new technology.

  12. Emerging small molecule drugs.

    PubMed

    Colin, Sophie; Chinetti-Gbaguidi, Giulia; Kuivenhoven, Jan A; Staels, Bart

    2015-01-01

    Dyslipidaemia is a major risk factor for cardiovascular diseases. Pharmacological lowering of LDL-C levels using statins reduces cardiovascular risk. However, a substantial residual risk persists especially in patients with type 2 diabetes mellitus. Because of the inverse association observed in epidemiological studies of HDL-C with the risk for cardiovascular diseases, novel therapeutic strategies to raise HDL-C levels or improve HDL functionality are developed as complementary therapy for cardiovascular diseases. However, until now most therapies targeting HDL-C levels failed in clinical trials because of side effects or absence of clinical benefits. This chapter will highlight the emerging small molecules currently developed and tested in clinical trials to pharmacologically modulate HDL-C and functionality including new CETP inhibitors (anacetrapib, evacetrapib), novel PPAR agonists (K-877, CER-002, DSP-8658, INT131 and GFT505), LXR agonists (ATI-111, LXR-623, XL-652) and RVX-208. PMID:25523004

  13. Biochips - Can molecules compute?

    NASA Astrophysics Data System (ADS)

    Tucker, J. B.

    1984-02-01

    In recent years the possibility has been considered to build 'biochip' computers, in which the silicon transistors of present machines would be replaced by large organic molecules or genetically engineered proteins. Two major advantages of such biochips over current devices would be related to vastly increased densities of computing elements, and entirely new styles of data processing, suited to such high-level tasks as pattern recognition and context-dependent analysis. The limitations of the semiconductor chip with respect to the density of elementary units due to size considerations and heat development could be overcome by making use of molecular switches. Attention is given to soliton switching, soliton logic, bulk molecular devices, analog biochips, 'intelligent' switches based on the employment of enzymes, robot vision, questions of biochip fabrication, protein engineering, and a strategy for the development of biochips.

  14. Forces in molecules.

    PubMed

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W

    2007-01-01

    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another? PMID:17328425

  15. Geranyl diphosphate synthase molecules, and nucleic acid molecules encoding same

    SciTech Connect

    Croteau, Rodney Bruce; Burke, Charles Cullen

    2008-06-24

    In one aspect, the present invention provides isolated nucleic acid molecules that each encode a geranyl diphosphate synthase protein, wherein each isolated nucleic acid molecule hybridizes to a nucleic acid molecule consisting of the sequence set forth in SEQ ID NO:1 under conditions of 5.times.SSC at 45.degree. C. for one hour. The present invention also provides isolated geranyl diphosphate synthase proteins, and methods for altering the level of expression of geranyl diphosphate synthase protein in a host cell.

  16. The Submillimeter-wave Rotational Spectra of Interstellar Molecules

    NASA Technical Reports Server (NTRS)

    Herbst, Eric; DeLucia, Frank C.; Butler, R. A. H.; Winnewisser, M.; Winnewisser, G.; Fuchs, U.; Groner, P.; Sastry, K. V. L. N.

    2002-01-01

    We discuss past and recent progress in our long-term laboratory program concerning the submillimeter-wave rotational spectroscopy of known and likely interstellar molecules, especially those associated with regions of high-mass star formation. Our program on the use of spectroscopy to study rotationally inelastic collisions of interstellar interest is also briefly mentioned.

  17. The Chloroplastic Protein THF1 Interacts with the Coiled-Coil Domain of the Disease Resistance Protein N′ and Regulates Light-Dependent Cell Death1[OPEN

    PubMed Central

    Sekine, Ken-Taro; Wallon, Thérèse; Sugiwaka, Yuji; Kobayashi, Kappei

    2016-01-01

    One branch of plant immunity is mediated through nucleotide-binding/Leu-rich repeat (NB-LRR) family proteins that recognize specific effectors encoded by pathogens. Members of the I2-like family constitute a well-conserved subgroup of NB-LRRs from Solanaceae possessing a coiled-coil (CC) domain at their N termini. We show here that the CC domains of several I2-like proteins are able to induce a hypersensitive response (HR), a form of programmed cell death associated with disease resistance. Using yeast two-hybrid screens, we identified the chloroplastic protein Thylakoid Formation1 (THF1) as an interacting partner for several I2-like CC domains. Co-immunoprecipitations and bimolecular fluorescence complementation assays confirmed that THF1 and I2-like CC domains interact in planta and that these interactions take place in the cytosol. Several HR-inducing I2-like CC domains have a negative effect on the accumulation of THF1, suggesting that the latter is destabilized by active CC domains. To confirm this model, we investigated N′, which recognizes the coat protein of most Tobamoviruses, as a prototypical member of the I2-like family. Transient expression and gene silencing data indicated that THF1 functions as a negative regulator of cell death and that activation of full-length N′ results in the destabilization of THF1. Consistent with the known function of THF1 in maintaining chloroplast homeostasis, we show that the HR induced by N′ is light-dependent. Together, our results define, to our knowledge, novel molecular mechanisms linking light and chloroplasts to the induction of cell death by a subgroup of NB-LRR proteins. PMID:26951433

  18. Organic Molecules in Meteorites

    NASA Astrophysics Data System (ADS)

    Martins, Zita

    2015-08-01

    Carbonaceous meteorites are primitive samples from the asteroid belt, containing 3-5wt% organic carbon. The exogenous delivery of organic matter by carbonaceous meteorites may have contributed to the organic inventory of the early Earth. The majority (>70%) of the meteoritic organic material consist of insoluble organic matter (IOM) [1]. The remaining meteoritic organic material (<30%) consists of a rich organic inventory of soluble organic compounds, including key compounds important in terrestrial biochemistry [2-4]. Different carbonaceous meteorites contain soluble organic molecules with different abundances and distributions, which may reflect the extension of aqueous alteration or thermal metamorphism on the meteorite parent bodies. Extensive aqueous alteration on the meteorite parent body may result on 1) the decomposition of α-amino acids [5, 6]; 2) synthesis of β- and γ-amino acids [2, 6-9]; 3) higher relative abundances of alkylated polycyclic aromatic hydrocarbons (PAHs) [6, 10]; and 4) higher L-enantiomer excess (Lee) value of isovaline [6, 11, 12].The soluble organic content of carbonaceous meteorites may also have a contribution from Fischer-Tropsch/Haber-Bosch type gas-grain reactions after the meteorite parent body cooled to lower temperatures [13, 14].The analysis of the abundances and distribution of the organic molecules present in meteorites helps to determine the physical and chemical conditions of the early solar system, and the prebiotic organic compounds available on the early Earth.[1] Cody and Alexander (2005) GCA 69, 1085. [2] Cronin and Chang (1993) in: The Chemistry of Life’s Origin. pp. 209-258. [3] Martins and Sephton (2009) in: Amino acids, peptides and proteins in organic chemistry. pp. 1-42. [4] Martins (2011) Elements 7, 35. [5] Botta et al. (2007) MAPS 42, 81. [6] Martins et al. (2015) MAPS, in press. [7] Cooper and Cronin (1995) GCA 59, 1003. [8] Glavin et al. (2006) MAPS. 41, 889. [9] Glavin et al. (2011) MAPS 45, 1948. [10

  19. Electrochromic graphene molecules.

    PubMed

    Ji, Zhiqiang; Doorn, Stephen K; Sykora, Milan

    2015-04-28

    Polyclic aromatic hydrocarbons also called Graphene Molecules (GMs), with chemical composition C132H36(COOH)2 were synthesized in situ on the surface of transparent nanocrystalline indium tin oxide (nc-ITO) electrodes and their electronic structure was studied electrochemically and spectro-electrochemically. Variations in the potential applied onto the nc-ITO/GM electrodes induce only small changes in the observed current, but they produce dramatic changes in the absorption of the GMs, which are associated with their oxidation and reduction. Analysis of the absorption changes using a modified Nernst equation is used to determine standard potentials associated with the individual charge transfer processes. For the GMs prepared here, these were found to be E1,ox(0) = 0.77 ± 0.01 V and E2,ox(0) = 1.24 ± 0.02 V vs NHE for the first and second oxidation and E1,red(0) = -1.50 ± 0.04 V for the first reduction. The charge transfer processes are found to be nonideal. The nonideality factors associated with the oxidation and reduction processes are attributed to strong interactions between the GM redox centers. Under the conditions of potential cycling, GMs show rapid (seconds) color change with high contrast and stability. An electrochromic application is demonstrated wherein the GMs are used as the optically active component. PMID:25768313

  20. Electrochromic Graphene Molecules

    DOE PAGESBeta

    Ji, Zhiqiang; Doorn, Stephen K.; Sykora, Milan

    2015-03-13

    Polyclic aromatic hydrocarbons, also called Graphene Molecules (GMs), with chemical composition C132H36(COOH)2 were synthesized in-situ on the surface of transparent nanocrystaline indium tin oxide (nc-ITO) electrodes. Their electronic structure was studied electrochemically and spectro-electrochemically. Variations in the potential applied onto the nc-ITO/GM electrodes induce only small changes in the observed current but they produce dramatic changes in the absorption of the GMs, which are associated with their oxidation and reduction. Analysis of the absorption changes using modified Nernst equation is used to determine standard potentials associated with the individual charge transfer processes. For the GMs prepared here these were foundmore » to be E1,ox 0 = 0.77± 0.01 V and E2,ox 0 = 1.24 ± 0.02 V vs. NHE for the first and second oxidation and E1,red 0 = -1.50 ± 0.04 V for the first reduction. The charge transfer processes are found to be non-ideal. The non-ideality factors associated with the oxidation and reduction processes suggest presence of strong interactions between the GM redox centers. Under the conditions of potential cycling GMs show rapid (seconds) color change with high contrast and stability. An electrochromic application is demonstrated wherein the GMs are used as the optically active component.« less

  1. Reactions of oriented molecules.

    PubMed

    Brooks, P R

    1976-07-01

    Beams of oriented molecules have been used to directly study geometrical requirements in chemical reactions. These studies have shown that reactivity is much greater in some orientations than others and demonstrated the existence of steric effects. For some reactions portions of the orientation results are in good accord with traditional views of steric hindrance, but for others it is clear that our chemical intuition needs recalibrating. Indeed, the information gained from simultaneously orienting the reactants and observing the scattering angle of the products may lead to new insights about the detailed mechanism of certain reactions. Further work must be done to extend the scope and detail of the studies described here. More detailed information is needed on the CH(3)I reaction and the CF(3)I reaction. The effects of alkyl groups of various sizes and alkali metals of various sizes are of interest. In addition, reactions where a long-lived complex is formed should be studied to see if orientation is important. Finally, it would be of interest to apply the technique to the sort of reactions that led to our interest in the first place: the S(N)2 displacements in alkyl halides where the fascinating Walden inversion occurs. PMID:17793988

  2. Single molecule tracking

    DOEpatents

    Shera, E. Brooks

    1988-01-01

    A detection system is provided for identifying individual particles or molecules having characteristic emission in a flow train of the particles in a flow cell. A position sensitive sensor is located adjacent the flow cell in a position effective to detect the emissions from the particles within the flow cell and to assign spatial and temporal coordinates for the detected emissions. A computer is then enabled to predict spatial and temporal coordinates for the particle in the flow train as a function of a first detected emission. Comparison hardware or software then compares subsequent detected spatial and temporal coordinates with the predicted spatial and temporal coordinates to determine whether subsequently detected emissions originate from a particle in the train of particles. In one embodiment, the particles include fluorescent dyes which are excited to fluoresce a spectrum characteristic of the particular particle. Photones are emitted adjacent at least one microchannel plate sensor to enable spatial and temporal coordinates to be assigned. The effect of comparing detected coordinates with predicted coordinates is to define a moving sample volume which effectively precludes the effects of background emissions.

  3. Single molecule tracking

    DOEpatents

    Shera, E.B.

    1987-10-07

    A detection system is provided for identifying individual particles or molecules having characteristic emission in a flow train of the particles in a flow cell. A position sensitive sensor is located adjacent the flow cell in a position effective to detect the emissions from the particles within the flow cell and to assign spatial and temporal coordinates for the detected emissions. A computer is then enabled to predict spatial and temporal coordinates for the particle in the flow train as a function of a first detected emission. Comparison hardware or software then compares subsequent detected spatial and temporal coordinates with the predicted spatial and temporal coordinates to determine whether subsequently detected emissions originate from a particle in the train of particles. In one embodiment, the particles include fluorescent dyes which are excited to fluoresce a spectrum characteristic of the particular particle. Photons are emitted adjacent at least one microchannel plate sensor to enable spatial and temporal coordinates to be assigned. The effect of comparing detected coordinates with predicted coordinates is to define a moving sample volume which effectively precludes the effects of background emissions. 3 figs.

  4. Strongly interacting ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Gadway, Bryce; Yan, Bo

    2016-08-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole–dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  5. Adsorption kinetics of diatomic molecules.

    PubMed

    Burde, Jared T; Calbi, M Mercedes

    2014-05-01

    The adsorption dynamics of diatomic molecules on solid surfaces is examined by using a Kinetic Monte Carlo algorithm. Equilibration times at increasing loadings are obtained, and explained based on the elementary processes that lead to the formation of the adsorbed film. The ability of the molecules to change their orientation accelerates the overall uptake and leads to competitive kinetic behaviour between the different orientations. The dependence of the equilibration time on coverage follows the same decreasing trend obtained experimentally for ethane adsorption on closed-end carbon nanotube bundles. The exploration of molecule-molecule interaction effects on this trend provides relevant insights to understand the kinetic behaviour of other species, from simpler molecules to larger polyatomic molecules, adsorbing on surfaces with different binding strength. PMID:24654004

  6. Trapping Single Molecules by Dielectrophoresis

    NASA Astrophysics Data System (ADS)

    Hölzel, Ralph; Calander, Nils; Chiragwandi, Zackary; Willander, Magnus; Bier, Frank F.

    2005-09-01

    We have trapped single protein molecules of R-phycoerythrin in an aqueous solution by an alternating electric field. A radio frequency voltage is applied to sharp nanoelectrodes and hence produces a strong electric field gradient. The resulting dielectrophoretic forces attract freely diffusing protein molecules. Trapping takes place at the electrode tips. Switching off the field immediately releases the molecules. The electric field distribution is computed, and from this the dielectrophoretic response of the molecules is calculated using a standard polarization model. The resulting forces are compared to the impact of Brownian motion. Finally, we discuss the experimental observations on the basis of the model calculations.

  7. Aromatic molecules as spintronic devices

    SciTech Connect

    Ojeda, J. H.; Orellana, P. A.; Laroze, D.

    2014-03-14

    In this paper, we study the spin-dependent electron transport through aromatic molecular chains attached to two semi-infinite leads. We model this system taking into account different geometrical configurations which are all characterized by a tight binding Hamiltonian. Based on the Green's function approach with a Landauer formalism, we find spin-dependent transport in short aromatic molecules by applying external magnetic fields. Additionally, we find that the magnetoresistance of aromatic molecules can reach different values, which are dependent on the variations in the applied magnetic field, length of the molecules, and the interactions between the contacts and the aromatic molecule.

  8. Electrical Transport through Organic Molecules

    NASA Astrophysics Data System (ADS)

    Lau, C. N.; Chang, Shun-Chi; Williams, Stan

    2003-03-01

    We investigate electrical transport properties of single organic molecules using electromigration break junctions[1]. A self-assembled monolayer of various organic molecules such as 1,4-di(phenylethynyl-4'-methanethiol)benzene was grown on narrow metal wires, and single or a few molecules were incorporated into the junctions which were created by applying a large voltage and breaking the wires. The transport properties of these molecules were then measured at low temperatures. Latest experimental results will be discussed. [1] Park, J. et al, Nature, 417, 722 (2002); Liang W. et al, Nature, 417, 725 (2002).

  9. Electrochromic Graphene Molecules

    SciTech Connect

    Ji, Zhiqiang; Doorn, Stephen K.; Sykora, Milan

    2015-03-13

    Polyclic aromatic hydrocarbons, also called Graphene Molecules (GMs), with chemical composition C132H36(COOH)2 were synthesized in-situ on the surface of transparent nanocrystaline indium tin oxide (nc-ITO) electrodes. Their electronic structure was studied electrochemically and spectro-electrochemically. Variations in the potential applied onto the nc-ITO/GM electrodes induce only small changes in the observed current but they produce dramatic changes in the absorption of the GMs, which are associated with their oxidation and reduction. Analysis of the absorption changes using modified Nernst equation is used to determine standard potentials associated with the individual charge transfer processes. For the GMs prepared here these were found to be E1,ox 0 = 0.77± 0.01 V and E2,ox 0 = 1.24 ± 0.02 V vs. NHE for the first and second oxidation and E1,red 0 = -1.50 ± 0.04 V for the first reduction. The charge transfer processes are found to be non-ideal. The non-ideality factors associated with the oxidation and reduction processes suggest presence of strong interactions between the GM redox centers. Under the conditions of potential cycling GMs show rapid (seconds) color change with high contrast and stability. An electrochromic application is demonstrated wherein the GMs are used as the optically active component.

  10. Adhesion molecules in cutaneous inflammation.

    PubMed

    Barker, J N

    1995-01-01

    As in other organs, leukocyte adhesion molecules and their ligands play a major role in cutaneous inflammatory events both by directing leukocyte trafficking and by their effects on antigen presentation. Skin biopsies of inflamed skin from patients with diseases such as as psoriasis or atopic dermatitis reveal up-regulation of endothelial cell expression of P- and E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. Studies of evolving lesions following UVB irradiation, Mantoux reaction or application of contact allergen, demonstrate that expression of these adhesion molecules parallels leukocyte infiltration into skin. When cutaneous inflammation is widespread (e.g. in erythroderma), soluble forms of these molecules are detectable in serum. In vitro studies predict that peptide mediators are important regulatory factors for endothelial adhesion molecules. Intradermal injection of the cytokines interleukin 1, tumour necrosis factor alpha and interferon gamma into normal human skin leads to induction of endothelial adhesion molecules with concomitant infiltration of leukocytes. In addition, neuropeptides rapidly induce P-selectin translocation to the cell membrane and expression of E-selectin. Adhesion molecules also play a crucial role as accessory molecules in the presentation of antigen to T lymphocytes by Langerhans' cells. Expression of selectin ligands by Langerhans' cells is up-regulated by various inflammatory stimuli, suggesting that adhesion molecules may be important in Langerhans' cell migration. The skin, because of its accessibility, is an ideal organ in which to study expression of adhesion molecules and their relationship to inflammatory events. Inflammatory skin diseases are common and inhibition of lymphocyte accumulation in skin is likely to prove of great therapeutic benefit. PMID:7587640

  11. Micro-Kelvin cold molecules.

    SciTech Connect

    Strecker, Kevin E.; Chandler, David W.

    2009-10-01

    We have developed a novel experimental technique for direct production of cold molecules using a combination of techniques from atomic optical and molecular physics and physical chemistry. The ability to produce samples of cold molecules has application in a broad spectrum of technical fields high-resolution spectroscopy, remote sensing, quantum computing, materials simulation, and understanding fundamental chemical dynamics. Researchers around the world are currently exploring many techniques for producing samples of cold molecules, but to-date these attempts have offered only limited success achieving milli-Kelvin temperatures with low densities. This Laboratory Directed Research and Development project is to develops a new experimental technique for producing micro-Kelvin temperature molecules via collisions with laser cooled samples of trapped atoms. The technique relies on near mass degenerate collisions between the molecule of interest and a laser cooled (micro-Kelvin) atom. A subset of collisions will transfer all (nearly all) of the kinetic energy from the 'hot' molecule, cooling the molecule at the expense of heating the atom. Further collisions with the remaining laser cooled atoms will thermally equilibrate the molecules to the micro-Kelvin temperature of the laser-cooled atoms.

  12. Featured Molecules: Sucrose and Vanillin

    NASA Astrophysics Data System (ADS)

    Coleman, William F.; Wildman, Randall J.

    2003-04-01

    The WebWare molecules of the month for April relate to the sense of taste. Apple Fool, the JCE Classroom Activity, mentions sucrose and vanillin and their use as flavorings. Fully manipulable (Chime) versions of these and other molecules are available at Only@JCE Online.

  13. Proregenerative Properties of ECM Molecules

    PubMed Central

    Plantman, Stefan

    2013-01-01

    After traumatic injuries to the nervous system, regrowing axons encounter a complex microenvironment where mechanisms that promote regeneration compete with inhibitory processes. Sprouting and axonal regrowth are key components of functional recovery but are often counteracted by inhibitory molecules. This review covers extracellular matrix molecules that support neuron axonal outgrowth. PMID:24195084

  14. Loosely-Bound Diatomic Molecules.

    ERIC Educational Resources Information Center

    Balfour, W. J.

    1979-01-01

    Discusses concept of covalent bonding as related to homonuclear diatomic molecules. Article draws attention to the existence of bound rare gas and alkaline earth diatomic molecules. Summarizes their molecular parameters and offers spectroscopic data. Strength and variation with distance of interatomic attractive forces is given. (Author/SA)

  15. Enzyme molecules in solitary confinement.

    PubMed

    Liebherr, Raphaela B; Gorris, Hans H

    2014-01-01

    Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities. PMID:25221867

  16. Magnetoassociation of KRb Feshbach molecules

    NASA Astrophysics Data System (ADS)

    Cumby, Tyler; Perreault, John; Shewmon, Ruth; Jin, Deborah

    2010-03-01

    I will discuss experiments in which we study the creation of ^40K^87Rb Feshbach molecules via magnetoassociation. We measure the molecule number as a function of the magnetic-field sweep rate through the interspecies Feshbach resonance and explore the dependence of association on the initial atom gas conditions. This study of the Feshbach molecule creation process may be relevant to the production of ultracold polar molecules, where magnetoassociated Feshbach molecules can be a crucial first step [1].[4pt] [1] K.-K. Ni, S. Ospelkaus, M. H. G. de Miranda, A. Peer, B. Neyenhuis, J. J. Zirbel, S. Kotochigova, P. S. Julienne, D. S. Jin, and J. Ye, Science, 2008, 322, 231- 235.

  17. Magnetoassociation of KRb Feshbach molecules

    NASA Astrophysics Data System (ADS)

    Cumby, Tyler; Perreault, John; Shewmon, Ruth; Jin, Deborah

    2010-03-01

    I will discuss experiments in which we study the creation of ^40K^87Rb Feshbach molecules via magnetoassociation. We measure the molecule number as a function of the magnetic-field sweep rate through the interspecies Feshbach resonance and explore the dependence of association on the initial atom gas conditions. This study of the Feshbach molecule creation process may be relevant to the production of ultracold polar molecules, where magnetoassociated Feshbach molecules can be a crucial first step [1].[4pt] [1] K.-K. Ni, S. Ospelkaus, M. H. G. de Miranda, A. Peer, B. Neyenhuis, J. J. Zirbel, S. Kotochigova, P. S. Julienne, D. S. Jin, and J. Ye, Science, 2008, 322, 231-235.

  18. Molecule-hugging graphene nanopores.

    PubMed

    Garaj, Slaven; Liu, Song; Golovchenko, Jene A; Branton, Daniel

    2013-07-23

    It has recently been recognized that solid-state nanopores in single-atomic-layer graphene membranes can be used to electronically detect and characterize single long charged polymer molecules. We have now fabricated nanopores in single-layer graphene that are closely matched to the diameter of a double-stranded DNA molecule. Ionic current signals during electrophoretically driven translocation of DNA through these nanopores were experimentally explored and theoretically modeled. Our experiments show that these nanopores have unusually high sensitivity (0.65 nA/Å) to extremely small changes in the translocating molecule's outer diameter. Such atomically short graphene nanopores can also resolve nanoscale-spaced molecular structures along the length of a polymer, but do so with greatest sensitivity only when the pore and molecule diameters are closely matched. Modeling confirms that our most closely matched pores have an inherent resolution of ≤ 0.6 nm along the length of the molecule. PMID:23836648

  19. Cold molecules, collisions and reactions

    NASA Astrophysics Data System (ADS)

    Hecker Denschlag, Johannes

    2016-05-01

    I will report on recent experiments of my group where we have been studying the formation of ultracold diatomic molecules and their subsequent inelastic/reactive collisions. For example, in one of these experiments we investigate collisions of triplet Rb2 molecules in the rovibrational ground state. We observe fast molecular loss and compare the measured loss rates to predictions based on universality. In another set of experiments we investigate the formation of (BaRb)+ molecules after three-body recombination of a single Ba+ ion with two Rb atoms in an ultracold gas of Rb atoms. Our investigations indicate that the formed (BaRb)+ molecules are weakly bound and that several secondary processes take place ranging from photodissociation of the (BaRb)+ molecule to reactive collisions with Rb atoms. I will explain how we can experimentally distinguish these processes and what the typical reaction rates are. Support from the German Research foundation DFG and the European Community is acknowledged.

  20. Single Molecule Electronics and Devices

    PubMed Central

    Tsutsui, Makusu; Taniguchi, Masateru

    2012-01-01

    The manufacture of integrated circuits with single-molecule building blocks is a goal of molecular electronics. While research in the past has been limited to bulk experiments on self-assembled monolayers, advances in technology have now enabled us to fabricate single-molecule junctions. This has led to significant progress in understanding electron transport in molecular systems at the single-molecule level and the concomitant emergence of new device concepts. Here, we review recent developments in this field. We summarize the methods currently used to form metal-molecule-metal structures and some single-molecule techniques essential for characterizing molecular junctions such as inelastic electron tunnelling spectroscopy. We then highlight several important achievements, including demonstration of single-molecule diodes, transistors, and switches that make use of electrical, photo, and mechanical stimulation to control the electron transport. We also discuss intriguing issues to be addressed further in the future such as heat and thermoelectric transport in an individual molecule. PMID:22969345

  1. Quantum transport through aromatic molecules

    SciTech Connect

    Ojeda, J. H.; Rey-González, R. R.; Laroze, D.

    2013-12-07

    In this paper, we study the electronic transport properties through aromatic molecules connected to two semi-infinite leads. The molecules are in different geometrical configurations including arrays. Using a nearest neighbor tight-binding approach, the transport properties are analyzed into a Green's function technique within a real-space renormalization scheme. We calculate the transmission probability and the Current-Voltage characteristics as a function of a molecule-leads coupling parameter. Our results show different transport regimes for these systems, exhibiting metal-semiconductor-insulator transitions and the possibility to employ them in molecular devices.

  2. Organic heterocyclic molecules become superalkalis.

    PubMed

    Reddy, G Naaresh; Giri, Santanab

    2016-09-21

    An organic molecule which behaves like a superalkali has been designed from an aromatic heterocyclic molecule, pyrrole. Using first-principles calculation and a systematic two-step approach, we can have superalkali molecules with a low ionization energy, even lower than that of Cs. Couple cluster (CCSD) calculation reveals that a new heterocycle, C3N2(CH3)5 derived from a well-known aromatic heterocycle, pyrrole (C4H5N) has an ionization energy close to 3.0 eV. A molecular dynamics calculation on C3N2(CH3)5 reveals that the structure is dynamically stable. PMID:27530344

  3. Nonsequential double ionization of molecules

    SciTech Connect

    Prauzner-Bechcicki, Jakub S.; Sacha, Krzysztof; Zakrzewski, Jakub; Eckhardt, Bruno

    2005-03-01

    Double ionization of diatomic molecules by short linearly polarized laser pulses is analyzed. We consider the final stage of the ionization process, that is the decay of a highly excited two electron molecule, which is formed after rescattering. The saddles of the effective adiabatic potential energy close to which simultaneous escape of electrons takes place are identified. Numerical simulations of the ionization of molecules show that the process can be dominated by either sequential or nonsequential events. In order to increase the ratio of nonsequential to sequential ionizations very short laser pulses should be applied.

  4. Resolving metal-molecule interfaces at single-molecule junctions

    PubMed Central

    Komoto, Yuki; Fujii, Shintaro; Nakamura, Hisao; Tada, Tomofumi; Nishino, Tomoaki; Kiguchi, Manabu

    2016-01-01

    Electronic and structural detail at the electrode-molecule interface have a significant influence on charge transport across molecular junctions. Despite the decisive role of the metal-molecule interface, a complete electronic and structural characterization of the interface remains a challenge. This is in no small part due to current experimental limitations. Here, we present a comprehensive approach to obtain a detailed description of the metal-molecule interface in single-molecule junctions, based on current-voltage (I-V) measurements. Contrary to conventional conductance studies, this I-V approach provides a correlated statistical description of both, the degree of electronic coupling across the metal-molecule interface, and the energy alignment between the conduction orbital and the Fermi level of the electrode. This exhaustive statistical approach was employed to study single-molecule junctions of 1,4-benzenediamine (BDA), 1,4-butanediamine (C4DA), and 1,4-benzenedithiol (BDT). A single interfacial configuration was observed for both BDA and C4DA junctions, while three different interfacial arrangements were resolved for BDT. This multiplicity is due to different molecular adsorption sites on the Au surface namely on-top, hollow, and bridge. Furthermore, C4DA junctions present a fluctuating I-V curve arising from the greater conformational freedom of the saturated alkyl chain, in sharp contrast with the rigid aromatic backbone of both BDA and BDT. PMID:27221947

  5. Resolving metal-molecule interfaces at single-molecule junctions

    NASA Astrophysics Data System (ADS)

    Komoto, Yuki; Fujii, Shintaro; Nakamura, Hisao; Tada, Tomofumi; Nishino, Tomoaki; Kiguchi, Manabu

    2016-05-01

    Electronic and structural detail at the electrode-molecule interface have a significant influence on charge transport across molecular junctions. Despite the decisive role of the metal-molecule interface, a complete electronic and structural characterization of the interface remains a challenge. This is in no small part due to current experimental limitations. Here, we present a comprehensive approach to obtain a detailed description of the metal-molecule interface in single-molecule junctions, based on current-voltage (I-V) measurements. Contrary to conventional conductance studies, this I-V approach provides a correlated statistical description of both, the degree of electronic coupling across the metal-molecule interface, and the energy alignment between the conduction orbital and the Fermi level of the electrode. This exhaustive statistical approach was employed to study single-molecule junctions of 1,4-benzenediamine (BDA), 1,4-butanediamine (C4DA), and 1,4-benzenedithiol (BDT). A single interfacial configuration was observed for both BDA and C4DA junctions, while three different interfacial arrangements were resolved for BDT. This multiplicity is due to different molecular adsorption sites on the Au surface namely on-top, hollow, and bridge. Furthermore, C4DA junctions present a fluctuating I-V curve arising from the greater conformational freedom of the saturated alkyl chain, in sharp contrast with the rigid aromatic backbone of both BDA and BDT.

  6. Ab initio calculations of the photoionization of diatomic molecules

    NASA Astrophysics Data System (ADS)

    Lefebvre-Brion, Helene; Raşeev, Georges

    2003-01-01

    A review is presented of the calculation of photoionization spectra, particularly in the spectral range where electron autoionization of diatomic molecules takes place. In addition to some interesting results obtained over years that compare favourably with experiment, the emphasis here is put on the relation between the methods developed for the calculation of observables associated with the continuum energy spectrum of the electrons and the Alchemy system of programs. This system of programs serves as a basis for initial and intermediate calculations. The examples presented show that diatomic molecules not only in gas phase but also oriented in space or physisorbed at surfaces may be studied readily.

  7. Biomedical applications of single molecule detection

    NASA Astrophysics Data System (ADS)

    Kelso, D. M.

    1997-05-01

    The search for increased sensitivity of bio-analytical techniques has recently shifted from signal generation to detection. While enzyme amplifiers and chemiluminescent reporters developed by chemists over the last two decades gradually moved detection limits to the attomol level, it has taken engineers only a few years to reach single- molecule sensitivity with the development of new instrumentation. A number of different approaches have successfully achieved single-molecule fluorescence detection including confocal and near-field scanning optical microscopy, photon-counting cameras, fluorescence- correlation and time-gated spectroscopy. They detect labels immobilized on substrates, diffusing in solution and flowing in electro-osmotic and hydrodynamically focused streams. Biotechnology has created numerous application s for single- molecule detection. In research labs, it can dramatically increase the rate of DNA sequencing, screen libraries for products of directed evolution, and characterize compounds in drug discovery programs. In medical diagnostics, ultra- sensitive detection technologies can be used for genetic screening, detection of infectious diseases, or multi- analyte profiles. It can be applied to immunoassays as well as DNA or RNA hybridization assays.

  8. Moving Molecules and Mothball Madness.

    ERIC Educational Resources Information Center

    Strain, John

    1993-01-01

    Describes concrete demonstrations on the states of matter. In the first demonstration, students represent molecules; and, in the second demonstration, moth balls are heated to produce a change of state. (PR)

  9. Surface chemistry of deuterated molecules

    NASA Astrophysics Data System (ADS)

    Tielens, A. G. G. M.

    1983-03-01

    The chemical composition of grain mantles is calculated in order to determine the concentration of deuterated molecules relative to their hydrogenated counterparts in grain mantles. The computation takes into account reactions involving deuterium in the gas phase and on grain surfaces. The results show that the abundance of deuterium molecules in grain mantles is much higher than expected on the basis of the cosmic abundance ratio of D to H. HDCO has a relatively high abundance in grain mantles as compared to other deuterated molecules, due to the fact that H abstraction from HDCO has a lower activation barrier than D abstraction. The infrared characteristics of the calculated grain mantles are discussed and observational tests of the model calcultions are suggested. The contribution of grain surface chemistry to the concentration of molecules in the gas phase is briefly considered.

  10. Cobalt single-molecule magnet

    NASA Astrophysics Data System (ADS)

    Yang, En-Che; Hendrickson, David N.; Wernsdorfer, Wolfgang; Nakano, Motohiro; Zakharov, Lev N.; Sommer, Roger D.; Rheingold, Arnold L.; Ledezma-Gairaud, Marisol; Christou, George

    2002-05-01

    A cobalt molecule that functions as a single-molecule magnet, [Co4(hmp)4(MeOH)4Cl4], where hmp- is the anion of hydroxymethylpyridine, is reported. The core of the molecule consists of four Co(II) cations and four hmp- oxygen atom ions at the corners of a cube. Variable-field and variable-temperature magnetization data have been analyzed to establish that the molecule has a S=6 ground state with considerable negative magnetoanisotropy. Single-ion zero-field interactions (DSz2) at each cobalt ion are the origin of the negative magnetoanisotropy. A single crystal of the compound was studied by means of a micro-superconducting quantum interference device magnetometer in the range of 0.040-1.0 K. Hysteresis was found in the magnetization versus magnetic field response of this single crystal.

  11. Spin tunneling in magnetic molecules

    NASA Astrophysics Data System (ADS)

    Kececioglu, Ersin

    In this thesis, we will focus on spin tunneling in a family of systems called magnetic molecules such as Fe8 and Mn12. This is comparatively new, in relation to other tunneling problems. Many issues are not completely solved and/or understood yet. The magnetic molecule Fe 8 has been observed to have a rich pattern of degeneracies in its magnetic spectrum. We focus on these degeneracies from several points of view. We start with the simplest anisotropy Hamiltonian to describe the Fe 8 molecule and extend our discussion to include higher order anisotropy terms. We give analytical expressions as much as we can, for the degeneracies in the semi-classical limit in both cases. We reintroduce jump instantons to the instanton formalism. Finally, we discuss the effect of the environment on the molecule. Our results, for all different models and techniques, agree well with both experimental and numerical results.

  12. Molecule-hugging graphene nanopores

    PubMed Central

    Garaj, Slaven; Liu, Song; Golovchenko, Jene A.; Branton, Daniel

    2013-01-01

    It has recently been recognized that solid-state nanopores in single-atomic-layer graphene membranes can be used to electronically detect and characterize single long charged polymer molecules. We have now fabricated nanopores in single-layer graphene that are closely matched to the diameter of a double-stranded DNA molecule. Ionic current signals during electrophoretically driven translocation of DNA through these nanopores were experimentally explored and theoretically modeled. Our experiments show that these nanopores have unusually high sensitivity (0.65 nA/Å) to extremely small changes in the translocating molecule’s outer diameter. Such atomically short graphene nanopores can also resolve nanoscale-spaced molecular structures along the length of a polymer, but do so with greatest sensitivity only when the pore and molecule diameters are closely matched. Modeling confirms that our most closely matched pores have an inherent resolution of ≤0.6 nm along the length of the molecule. PMID:23836648

  13. Single-Molecule DNA Analysis

    NASA Astrophysics Data System (ADS)

    Efcavitch, J. William; Thompson, John F.

    2010-07-01

    The ability to detect single molecules of DNA or RNA has led to an extremely rich area of exploration of the single most important biomolecule in nature. In cases in which the nucleic acid molecules are tethered to a solid support, confined to a channel, or simply allowed to diffuse into a detection volume, novel techniques have been developed to manipulate the DNA and to examine properties such as structural dynamics and protein-DNA interactions. Beyond the analysis of the properties of nucleic acids themselves, single-molecule detection has enabled dramatic improvements in the throughput of DNA sequencing and holds promise for continuing progress. Both optical and nonoptical detection methods that use surfaces, nanopores, and zero-mode waveguides have been attempted, and one optically based instrument is already commercially available. The breadth of literature related to single-molecule DNA analysis is vast; this review focuses on a survey of efforts in molecular dynamics and nucleic acid sequencing.

  14. Fluorescence Microscopy of Single Molecules

    ERIC Educational Resources Information Center

    Zimmermann, Jan; van Dorp, Arthur; Renn, Alois

    2004-01-01

    The investigation of photochemistry and photophysics of individual quantum systems is described with the help of a wide-field fluorescence microscopy approach. The fluorescence single molecules are observed in real time.

  15. Collisional decoherence of polar molecules

    NASA Astrophysics Data System (ADS)

    Walter, Kai; Stickler, Benjamin A.; Hornberger, Klaus

    2016-06-01

    The quantum state of motion of a large and rotating polar molecule can lose coherence through the collisions with gas atoms. We show how the associated quantum master equation for the center of mass can be expressed in terms of the orientationally averaged differential and total scattering cross sections, for which we provide approximate analytic expressions. The master equation is then utilized to quantify collisional decoherence in a interference experiment with polar molecules.

  16. Nanochannel Based Single Molecule Recycling

    PubMed Central

    Lesoine, John F.; Venkataraman, Prahnesh A.; Maloney, Peter C.; Dumont, Mark

    2012-01-01

    We present a method for measuring the fluorescence from a single molecule hundreds of times without surface immobilization. The approach is based on the use of electroosmosis to repeatedly drive a single target molecule in a fused silica nanochannel through a stationary laser focus. Single molecule fluorescence detected during the transit time through the laser focus is used to repeatedly reverse the electrical potential controlling the flow direction. Our method does not rely on continuous observation and therefore is less susceptible to fluorescence blinking than existing fluorescence-based trapping schemes. The variation in the turnaround times can be used to measure the diffusion coefficient on a single molecule level. We demonstrate the ability to recycle both proteins and DNA in nanochannels and show that the procedure can be combined with single-pair Förster energy transfer. Nanochannel-based single molecule recycling holds promise for studying conformational dynamics on the same single molecule in solution and without surface tethering. PMID:22662745

  17. Temperature dependence of charge transport in conjugated single molecule junctions

    NASA Astrophysics Data System (ADS)

    Huisman, Eek; Kamenetska, Masha; Venkataraman, Latha

    2011-03-01

    Over the last decade, the break junction technique using a scanning tunneling microscope geometry has proven to be an important tool to understand electron transport through single molecule junctions. Here, we use this technique to probe transport through junctions at temperatures ranging from 5K to 300K. We study three amine-terminated (-NH2) conjugated molecules: a benzene, a biphenyl and a terphenyl derivative. We find that amine groups bind selectively to undercoordinate gold atoms gold all the way down to 5K, yielding single molecule junctions with well-defined conductances. Furthermore, we find that the conductance of a single molecule junction increases with temperature and we present a mechanism for this temperature dependent transport result. Funded by a Rubicon Grant from The Netherlands Organisation for Scientific Research (NWO) and the NSEC program of NSF under grant # CHE-0641523.

  18. Combining single-molecule manipulation and single-molecule detection.

    PubMed

    Cordova, Juan Carlos; Das, Dibyendu Kumar; Manning, Harris W; Lang, Matthew J

    2014-10-01

    Single molecule force manipulation combined with fluorescence techniques offers much promise in revealing mechanistic details of biomolecular machinery. Here, we review force-fluorescence microscopy, which combines the best features of manipulation and detection techniques. Three of the mainstay manipulation methods (optical traps, magnetic traps and atomic force microscopy) are discussed with respect to milestones in combination developments, in addition to highlight recent contributions to the field. An overview of additional strategies is discussed, including fluorescence based force sensors for force measurement in vivo. Armed with recent exciting demonstrations of this technology, the field of combined single-molecule manipulation and single-molecule detection is poised to provide unprecedented views of molecular machinery. PMID:25255052

  19. Raman Optical Activity Spectra for Large Molecules through Molecules-in-Molecules Fragment-Based Approach.

    PubMed

    Jovan Jose, K V; Raghavachari, Krishnan

    2016-02-01

    We present an efficient method for the calculation of the Raman optical activity (ROA) spectra for large molecules through the molecules-in-molecules (MIM) fragment-based method. The relevant higher energy derivatives from smaller fragments are used to build the property tensors of the parent molecule to enable the extension of the MIM method for evaluating ROA spectra (MIM-ROA). Two factors were found to be particularly important in yielding accurate results. First, the link-atom tensor components are projected back onto the corresponding host and supporting atoms through the Jacobian projection method, yielding a mathematically rigorous method. Second, the long-range interactions between fragments are taken into account by using a less computationally expensive lower level of theory. The performance of the MIM-ROA model is calibrated on the enantiomeric pairs of 10 carbohydrate benchmark molecules, with strong intramolecular interactions. The vibrational frequencies and ROA intensities are accurately reproduced relative to the full, unfragmented, results for these systems. In addition, the MIM-ROA method is employed to predict the ROA spectra of d-maltose, α-D-cyclodextrin, and cryptophane-A, yielding spectra in excellent agreement with experiment. The accuracy and performance of the benchmark systems validate the MIM-ROA model for exploring ROA spectra of large molecules. PMID:26760444

  20. Measuring an antibody affinity distribution molecule by molecule

    SciTech Connect

    Bradbury, Andrew M; Werner, James H; Temirov, Jamshid

    2008-01-01

    Single molecule fluorescence mIcroscopy was used to observe the binding and unbinding of hapten decorated quantum dots with individual surface immobilized antibodies. The fluorescence time history from an individual antibody site can be used to calculate its binding affinity. While quantum dot blinking occurs during these measurements, we describe a simple empirical method to correct the apparent/observed affinity to account for the blinking contribution. The combination of many single molecule affinity measurements from different antibodies yields not only the average affinity, it directly measures the full shape and character of the surface affinity distribution function.

  1. Are solar UV-B- and UV-A-dependent gene expression and metabolite accumulation in Arabidopsis mediated by the stress response regulator RADICAL-INDUCED CELL DEATH1?

    PubMed

    Morales, Luis O; Brosché, Mikael; Vainonen, Julia P; Sipari, Nina; Lindfors, Anders V; Strid, Åke; Aphalo, Pedro J

    2015-05-01

    Wavelengths in the ultraviolet (UV) region of the solar spectrum, UV-B (280-315 nm) and UV-A (315-400 nm), are key environmental signals modifying several aspects of plant physiology. Despite significant advances in the understanding of plant responses to UV-B and the identification of signalling components involved, there is limited information on the molecular mechanisms that control UV-B signalling in plants under natural sunlight. Here, we aimed to corroborate the previous suggested role for RADICAL-INDUCED CELL DEATH1 (RCD1) in UV-B signalling under full spectrum sunlight. Wild-type Arabidopsis thaliana and the rcd1-1 mutant were used in an experimental design outdoors where UV-B and UV-A irradiances were manipulated using plastic films, and gene expression, PYRIDOXINE BIOSYNTHESIS1 (PDX1) accumulation and metabolite profiles were analysed in the leaves. At the level of transcription, RCD1 was not directly involved in the solar UV-B regulation of genes with functions in UV acclimation, hormone signalling and stress-related markers. Furthermore, RCD1 had no role on PDX1 accumulation but modulated the UV-B induction of flavonoid accumulation in leaves of Arabidopsis exposed to solar UV. We conclude that RCD1 does not play an active role in UV-B signalling but rather modulates UV-B responses under full spectrum sunlight. PMID:24689869

  2. Electron Collisions with Large Molecules

    NASA Astrophysics Data System (ADS)

    McKoy, Vincent

    2006-10-01

    In recent years, interest in electron-molecule collisions has increasingly shifted to large molecules. Applications within the semiconductor industry, for example, require electron collision data for molecules such as perfluorocyclobutane, while almost all biological applications involve macromolecules such as DNA. A significant development in recent years has been the realization that slow electrons can directly damage DNA. This discovery has spurred studies of low-energy collisions with the constituents of DNA, including the bases, deoxyribose, the phosphate, and larger moieties assembled from them. In semiconductor applications, a key goal is development of electron cross section sets for plasma chemistry modeling, while biological studies are largely focused on understanding the role of localized resonances in inducing DNA strand breaks. Accurate calculations of low-energy electron collisions with polyatomic molecules are computationally demanding because of the low symmetry and inherent many-electron nature of the problem; moreover, the computational requirements scale rapidly with the size of the molecule. To pursue such studies, we have adapted our computational procedure, known as the Schwinger multichannel method, to run efficiently on highly parallel computers. In this talk, we will present some of our recent results for fluorocarbon etchants used in the semiconductor industry and for constituents of DNA and RNA. In collaboration with Carl Winstead, California Institute of Technology.

  3. Spectroscopic modeling of water molecule

    NASA Astrophysics Data System (ADS)

    Danylo, R. I.; Okhrimenko, B. A.

    2013-12-01

    This research is devoted to the vibrational spectroscopy inverse problem solution that gives a possibility to design a molecule and make conclusions about its geometry. The valence angle finding based on the usage of inverse spectral vibrational spectroscopy problem is a well-known task. 3N-matrix method was chosen to solve the proposed task. The usage of this method permits to make no assumptions about the molecule force field, besides it can be applied to molecules of matter in liquid state. Anharmonicity constants assessment is an important part of the valence angle finding. The reduction to zero vibrations is necessary because used matrix analytical expression were found in the harmonic approach. In order to find the single-valued inverse spectral problem of vibrational spectroscopy solution a shape parameter characterizing "mixing" of ω1 and ω2 vibrations forms must be found. The minimum of such a function Υ called a divergence parameter was found. This function characterizes method's accuracy. The valence angle assessment was reduced to the divergence parameter minimization. The β value concerning divergence parameter minimum was interpreted as the desired valence angle. The proposed method was applied for water molecule in liquid state: β = (88,8 ±1,7)° . The found angle fits the water molecule nearest surrounding tetrahedral model including hydrogen bond curvature in the first approximation.

  4. Room temperature single molecule microscopes

    SciTech Connect

    Ambrose, W.P.; Goodwin, P.M.; Enderlein, G.; Semin, D.J.; Keller, R.A.

    1997-12-31

    We have developed three capabilities to image the locations of and interrogate immobilized single fluorescent molecules: near-field scanning optical, confocal scanning optical, and wide-field epi-fluorescence microscopy. Each microscopy has its own advantages. Near-field illumination can beat the diffraction limit. Confocal microscopy has high brightness and temporal resolution. Wide-field has the quickest (parallel) imaging capability. With confocal microscopy, we have verified that single fluorescent spots in our images are due to single molecules by observing photon antibunching. Using all three microscopies, we have observed that xanthene molecules dispersed on dry silica curiously exhibit intensity fluctuations on millisecond to minute time scales. We are exploring the connection between the intensity fluctuations and fluctuations in individual photophysical parameters. The fluorescence lifetimes of Rhodamine 6G on silica fluctuate. The complex nature of the intensity and lifetime fluctuations is consistent with a mechanism that perturbs more than one photophysical parameter.

  5. Guidance molecules in lung cancer

    PubMed Central

    Nasarre, Patrick; Potiron, Vincent; Drabkin, Harry

    2010-01-01

    Guidance molecules were first described in the nervous system to control axon outgrowth direction. They are also widely expressed outside the nervous system where they control cell migration, tissue development and establishment of the vascular network. In addition, they are involved in cancer development, tumor angiogenesis and metastasis. This review is primarily focused on their functions in lung cancer and their involvement in lung development is also presented. Five guidance molecule families and their corresponding receptors are described, including the semaphorins/neuropilins/plexins, ephrins and Eph receptors, netrin/DCC/UNC5, Slit/Robo and Notch/Delta. In addition, the possibility to target these molecules as a therapeutic approach in cancer is discussed. PMID:20139699

  6. Phase structure of soliton molecules

    SciTech Connect

    Hause, A.; Hartwig, H.; Seifert, B.; Stolz, H.; Boehm, M.; Mitschke, F.

    2007-06-15

    Temporal optical soliton molecules were recently demonstrated; they potentially allow further increase of data rates in optical telecommunication. Their binding mechanism relies on the internal phases, but these have not been experimentally accessible so far. Conventional frequency-resolved optical gating techniques are not suited for measurement of their phase profile: Their algorithms fail to converge due to zeros both in their temporal and their spectral profile. We show that the VAMPIRE (very advanced method of phase and intensity retrieval of E-fields) method performs reliably. With VAMPIRE the phase profile of soliton molecules has been measured, and further insight into the mechanism is obtained.

  7. Phase structure of soliton molecules

    NASA Astrophysics Data System (ADS)

    Hause, A.; Hartwig, H.; Seifert, B.; Stolz, H.; Böhm, M.; Mitschke, F.

    2007-06-01

    Temporal optical soliton molecules were recently demonstrated; they potentially allow further increase of data rates in optical telecommunication. Their binding mechanism relies on the internal phases, but these have not been experimentally accessible so far. Conventional frequency-resolved optical gating techniques are not suited for measurement of their phase profile: Their algorithms fail to converge due to zeros both in their temporal and their spectral profile. We show that the VAMPIRE (very advanced method of phase and intensity retrieval of E -fields) method performs reliably. With VAMPIRE the phase profile of soliton molecules has been measured, and further insight into the mechanism is obtained.

  8. Orbital molecules in electronic materials

    SciTech Connect

    Attfield, J. Paul

    2015-04-01

    Orbital molecules are made up of coupled orbital states on several metal ions within an orbitally ordered (and sometimes also charge-ordered) solid such as a transition metal oxide. Spin-singlet dimers are known in many materials, but recent discoveries of more exotic species such as 18-electron heptamers in AlV{sub 2}O{sub 4} and magnetic 3-atom trimerons in magnetite (Fe{sub 3}O{sub 4}) have shown that orbital molecules constitute a general new class of quantum electronic states in solids.

  9. Dipolar molecules in optical lattices.

    PubMed

    Sowiński, Tomasz; Dutta, Omjyoti; Hauke, Philipp; Tagliacozzo, Luca; Lewenstein, Maciej

    2012-03-16

    We study the extended Bose-Hubbard model describing an ultracold gas of dipolar molecules in an optical lattice, taking into account all on-site and nearest-neighbor interactions, including occupation-dependent tunneling and pair tunneling terms. Using exact diagonalization and the multiscale entanglement renormalization ansatz, we show that these terms can destroy insulating phases and lead to novel quantum phases. These considerable changes of the phase diagram have to be taken into account in upcoming experiments with dipolar molecules. PMID:22540482

  10. Nonadiabatic reaction of energetic molecules.

    PubMed

    Bhattacharya, Atanu; Guo, Yuanqing; Bernstein, Elliot R

    2010-12-21

    Energetic materials store a large amount of chemical energy that can be readily converted into mechanical energy via decomposition. A number of different ignition processes such as sparks, shocks, heat, or arcs can initiate the excited electronic state decomposition of energetic materials. Experiments have demonstrated the essential role of excited electronic state decomposition in the energy conversion process. A full understanding of the mechanisms for the decomposition of energetic materials from excited electronic states will require the investigation and analysis of the specific topography of the excited electronic potential energy surfaces (PESs) of these molecules. The crossing of multidimensional electronic PESs creates a funnel-like topography, known as conical intersections (CIs). CIs are well established as a controlling factor in the excited electronic state decomposition of polyatomic molecules. This Account summarizes our current understanding of the nonadiabatic unimolecular chemistry of energetic materials through CIs and presents the essential role of CIs in the determination of decomposition pathways of these energetic systems. Because of the involvement of more than one PES, a decomposition process involving CIs is an electronically nonadiabatic mechanism. Based on our experimental observations and theoretical calculations, we find that a nonadiabatic reaction through CIs dominates the initial decomposition process of energetic materials from excited electronic states. Although the nonadiabatic behavior of some polyatomic molecules has been well studied, the role of nonadiabatic reactions in the excited electronic state decomposition of energetic molecules has not been well investigated. We use both nanosecond energy-resolved and femtosecond time-resolved spectroscopic techniques to determine the decomposition mechanism and dynamics of energetic species experimentally. Subsequently, we employ multiconfigurational methodologies (such as, CASSCF

  11. Piezoresistivity in single DNA molecules

    PubMed Central

    Bruot, Christopher; Palma, Julio L.; Xiang, Limin; Mujica, Vladimiro; Ratner, Mark A.; Tao, Nongjian

    2015-01-01

    Piezoresistivity is a fundamental property of materials that has found many device applications. Here we report piezoresistivity in double helical DNA molecules. By studying the dependence of molecular conductance and piezoresistivity of single DNA molecules with different sequences and lengths, and performing molecular orbital calculations, we show that the piezoresistivity of DNA is caused by force-induced changes in the π–π electronic coupling between neighbouring bases, and in the activation energy of hole hopping. We describe the results in terms of thermal activated hopping model together with the ladder-based mechanical model for DNA proposed by de Gennes. PMID:26337293

  12. Piezoresistivity in single DNA molecules

    NASA Astrophysics Data System (ADS)

    Bruot, Christopher; Palma, Julio L.; Xiang, Limin; Mujica, Vladimiro; Ratner, Mark A.; Tao, Nongjian

    2015-09-01

    Piezoresistivity is a fundamental property of materials that has found many device applications. Here we report piezoresistivity in double helical DNA molecules. By studying the dependence of molecular conductance and piezoresistivity of single DNA molecules with different sequences and lengths, and performing molecular orbital calculations, we show that the piezoresistivity of DNA is caused by force-induced changes in the π-π electronic coupling between neighbouring bases, and in the activation energy of hole hopping. We describe the results in terms of thermal activated hopping model together with the ladder-based mechanical model for DNA proposed by de Gennes.

  13. Piezoresistivity in single DNA molecules.

    PubMed

    Bruot, Christopher; Palma, Julio L; Xiang, Limin; Mujica, Vladimiro; Ratner, Mark A; Tao, Nongjian

    2015-01-01

    Piezoresistivity is a fundamental property of materials that has found many device applications. Here we report piezoresistivity in double helical DNA molecules. By studying the dependence of molecular conductance and piezoresistivity of single DNA molecules with different sequences and lengths, and performing molecular orbital calculations, we show that the piezoresistivity of DNA is caused by force-induced changes in the π-π electronic coupling between neighbouring bases, and in the activation energy of hole hopping. We describe the results in terms of thermal activated hopping model together with the ladder-based mechanical model for DNA proposed by de Gennes. PMID:26337293

  14. Monitoring Molecules: Insights and Progress

    PubMed Central

    2015-01-01

    In August, 2014, neuroscientists and physical scientists gathered together on the campus of the University of California, Los Angeles to discuss how to monitor molecules in neuroscience. This field has seen significant growth since its inception in the 1970s. Here, the advances in this field are documented, including its advance into understanding the actions that specific neurotransmitters mediate during behavior. PMID:25514501

  15. Nucleic Acids as Information Molecules.

    ERIC Educational Resources Information Center

    McInerney, Joseph D.

    1996-01-01

    Presents an activity that aims at enabling students to recognize that DNA and RNA are information molecules whose function is to store, copy, and make available the information in biological systems, without feeling overwhelmed by the specialized vocabulary and the minutia of the central dogma. (JRH)

  16. Nanodevices for Single Molecule Studies

    NASA Astrophysics Data System (ADS)

    Craighead, H. G.; Stavis, S. M.; Samiee, K. T.

    During the last two decades, biotechnology research has resulted in progress in fields as diverse as the life sciences, agriculture and healthcare. While existing technology enables the analysis of a variety of biological systems, new tools are needed for increasing the efficiency of current methods, and for developing new ones altogether. Interest has grown in single molecule analysis for these reasons.

  17. Dialkylresorcinols as bacterial signaling molecules

    PubMed Central

    Brameyer, Sophie; Kresovic, Darko; Bode, Helge B.; Heermann, Ralf

    2015-01-01

    It is well recognized that bacteria communicate via small diffusible molecules, a process termed quorum sensing. The best understood quorum sensing systems are those that use acylated homoserine lactones (AHLs) for communication. The prototype of those systems consists of a LuxI-like AHL synthase and a cognate LuxR receptor that detects the signal. However, many proteobacteria possess LuxR receptors, yet lack any LuxI-type synthase, and thus these receptors are referred to as LuxR orphans or solos. In addition to the well-known AHLs, little is known about the signaling molecules that are sensed by LuxR solos. Here, we describe a novel cell–cell communication system in the insect and human pathogen Photorhabdus asymbiotica. We identified the LuxR homolog PauR to sense dialkylresorcinols (DARs) and cyclohexanediones (CHDs) instead of AHLs as signals. The DarABC synthesis pathway produces the molecules, and the entire system emerged as important for virulence. Moreover, we have analyzed more than 90 different Photorhabdus strains by HPLC/MS and showed that these DARs and CHDs are specific to the human pathogen P. asymbiotica. On the basis of genomic evidence, 116 other bacterial species are putative DAR producers, among them many human pathogens. Therefore, we discuss the possibility of DARs as novel and widespread bacterial signaling molecules and show that bacterial cell–cell communication goes far beyond AHL signaling in nature. PMID:25550519

  18. Designing a small molecule erythropoietin mimetic.

    PubMed

    Guarnieri, Frank

    2015-01-01

    led to the creation of an in vitro active molecule. The combination of changing functional groups to enable good pharmacokinetics, while not changing the key intrinsic symmetry properties were never seriously pursued at Locus and the program died. Investigations into how red blood cells are created have occupied many prominent researchers for the entire twentieth century. In the second half of the century EPO was discovered and by the end of the century it became a blockbuster commercial product that launched the biotech revolution. PMID:25709041

  19. Size selective hydrophobic adsorbent for organic molecules

    NASA Technical Reports Server (NTRS)

    Sharma, Pramod K. (Inventor); Hickey, Gregory S. (Inventor)

    1997-01-01

    The present invention relates to an adsorbent formed by the pyrolysis of a hydrophobic silica with a pore size greater than 5 .ANG., such as SILICALITE.TM., with a molecular sieving polymer precursor such as polyfurfuryl alcohol, polyacrylonitrile, polyvinylidene chloride, phenol-formaldehyde resin, polyvinylidene difluoride and mixtures thereof. Polyfurfuryl alcohol is the most preferred. The adsorbent produced by the pyrolysis has a silicon to carbon mole ratio of between about 10:1 and 1:3, and preferably about 2:1 to 1:2, most preferably 1:1. The pyrolysis is performed as a ramped temperature program between about 100.degree. and 800.degree. C., and preferably between about 100.degree. and 600.degree. C. The present invention also relates to a method for selectively adsorbing organic molecules having a molecular size (mean molecular diameter) of between about 3 and 6 .ANG. comprising contacting a vapor containing the small organic molecules to be adsorbed with the adsorbent composition of the present invention.

  20. Photoabsorption and photodissociation of molecules important in the interstellar medium

    NASA Technical Reports Server (NTRS)

    Lee, L. C.

    1986-01-01

    In the period from May 15, 1985 to May 14, 1986, the photoabsorption and photodissociation cross sections of the interstellar radical of SO and the interstellar molecules of HCl, H2CO, and CH3CN were measured and the results were reported in scientific papers. In the meantime, a windowless apparatus is used to measure the photoabsorption and photodissociation cross sections of CO in the 90-105 nm region. The optical data obtained in this research program are needed for the determination of the formation and destruction rates of molecules and radicals in the interstellar medium. Accomplishments in this research period are summarized below.

  1. Validating and understanding ring conformations using small molecule crystallographic data.

    PubMed

    Cottrell, Simon J; Olsson, Tjelvar S G; Taylor, Robin; Cole, Jason C; Liebeschuetz, John W

    2012-04-23

    Understanding the conformational preferences of ring structures is fundamental to structure-based drug design. Although the Cambridge Structural Database (CSD) provides information on the preferred conformations of small molecules, analyzing this data can be very time-consuming. In order to overcome this hurdle, tools have been developed for quickly extracting geometrical preferences from the CSD. Here we describe how the program Mogul has been extended to analyze and compare ring conformations, using a library derived from over 900 000 ring fragments in the CSD. We illustrate how these can be used to understand the conformational preferences of molecules in a crystal lattice and bound to proteins. PMID:22372622

  2. Structure factors for tunneling ionization rates of diatomic molecules

    SciTech Connect

    Saito, Ryoichi; Tolstikhin, Oleg I.; Madsen, Lars Bojer; Morishita, Toru

    2015-05-15

    Within the leading-order, single-active-electron, and frozen-nuclei approximation of the weak-field asymptotic theory, the rate of tunneling ionization of a molecule in an external static uniform electric field is determined by the structure factor for the highest occupied molecular orbital. We present the results of systematic calculations of structure factors for 40 homonuclear and heteronuclear diatomic molecules by the Hartree–Fock method using a numerical grid-based approach implemented in the program X2DHF.

  3. Quantum Monte Carlo for vibrating molecules

    SciTech Connect

    Brown, W.R. |

    1996-08-01

    Quantum Monte Carlo (QMC) has successfully computed the total electronic energies of atoms and molecules. The main goal of this work is to use correlation function quantum Monte Carlo (CFQMC) to compute the vibrational state energies of molecules given a potential energy surface (PES). In CFQMC, an ensemble of random walkers simulate the diffusion and branching processes of the imaginary-time time dependent Schroedinger equation in order to evaluate the matrix elements. The program QMCVIB was written to perform multi-state VMC and CFQMC calculations and employed for several calculations of the H{sub 2}O and C{sub 3} vibrational states, using 7 PES`s, 3 trial wavefunction forms, two methods of non-linear basis function parameter optimization, and on both serial and parallel computers. In order to construct accurate trial wavefunctions different wavefunctions forms were required for H{sub 2}O and C{sub 3}. In order to construct accurate trial wavefunctions for C{sub 3}, the non-linear parameters were optimized with respect to the sum of the energies of several low-lying vibrational states. In order to stabilize the statistical error estimates for C{sub 3} the Monte Carlo data was collected into blocks. Accurate vibrational state energies were computed using both serial and parallel QMCVIB programs. Comparison of vibrational state energies computed from the three C{sub 3} PES`s suggested that a non-linear equilibrium geometry PES is the most accurate and that discrete potential representations may be used to conveniently determine vibrational state energies.

  4. Cold collisions between boson or fermion molecules

    SciTech Connect

    Kajita, Masatoshi

    2004-01-01

    We theoretically investigate collisions between electrostatically trapped cold polar molecules and compare boson and fermion isotopes. Evaporative cooling seems possible for fermion molecules as the ratio of the collision loss cross section to the elastic collision cross section (R) gets smaller as the molecular temperature T lowers. With boson molecules, R gets larger as T lowers, which makes evaporative cooling difficult. The elastic collision cross section between fermion molecules can be larger than that for boson molecules with certain conditions.

  5. Dissociation energy of molecules in dense gases

    NASA Technical Reports Server (NTRS)

    Kunc, J. A.

    1992-01-01

    A general approach is presented for calculating the reduction of the dissociation energy of diatomic molecules immersed in a dense (n = less than 10 exp 22/cu cm) gas of molecules and atoms. The dissociation energy of a molecule in a dense gas differs from that of the molecule in vacuum because the intermolecular forces change the intramolecular dynamics of the molecule, and, consequently, the energy of the molecular bond.

  6. Atoms and Molecules. Physical Science in Action[TM]. Schlessinger Science Library. [Videotape].

    ERIC Educational Resources Information Center

    2000

    There are more than 20 million known substances in the universe, and they are all made of the same basic ingredients--atoms and molecules. In this fun and engaging program, kids will learn about the three main subatomic particles--protons, neutrons and electrons--as well as the forces that keep atoms and molecules together. They'll discover how…

  7. X(3872): charmonium or molecule?

    SciTech Connect

    Nefediev, A. V.

    2011-05-23

    A theoretical analysis of the recent experimental data from the Belle and BABAR Collaborations on the charmonium state X(3872) is performed. The analysis takes into account the proximity of an S-wave mesonic threshold and a possible presence of molecule component in the resonance wave function, finite width of the molecule constituents, and a possible interference in the final state. In particular, a model-independent approach is formulated, based on the Flatte parametrisation of near-threshold observables as well as on the Weinberg analysis of the nature of weakly bound systems generalised to the case of unstable constituents. Conclusion is made that the X(3872) is generated dynamically by a strong coupling of the bare {chi}{sub c1} charmonium to the DD-bar* hadronic channel, with a large admixture of the DD-bar* molecular component.

  8. Electrochemical detection of single molecules.

    PubMed

    Fan, F R; Bard, A J

    1995-02-10

    The electrochemical behavior of a single molecule can be observed by trapping a small volume of a dilute solution of the electroactive species between an ultramicroelectrode tip with a diameter of approximately 15 nanometers and a conductive substrate. A scanning electrochemical microscope was used to adjust the tip-substrate distance ( approximately 10 nanometers), and the oxidation of [(trimethylammonio)methyl] ferrocene (Cp(2)FeTMA(+)) to Cp(2)FeTMA(2+) was carried out. The response was stochastic, and anodic current peaks were observed as the molecule moved into and out of the electrode-substrate gap. Similar experiments were performed with a solution containing two redox species, ferrocene carboxylate (Cp(2)FeCOO(-)) and Os(bpy)(3)(2+) (bpy is 2,2'-bipyridyl). PMID:17813918

  9. Bioactive molecules from sea hares.

    PubMed

    Kamiya, H; Sakai, R; Jimbo, M

    2006-01-01

    Sea hares, belonging to the order Opisthobranchia, subclass Gastropoda, are mollusks that have attracted many researchers who are interested in the chemical defense mechanisms of these soft and "shell-less" snails. Numbers of small molecules of dietary origin have been isolated from sea hares and some have ecologically relevant activities, such as fish deterrent activity or toxicity. Recently, however, greater attention has been paid to biomedically interesting sea hare isolates such as dolastatins, a series of antitumor peptide/macrolides isolated from Dolabella auricularia. Another series of bioactive peptide/macrolides, as represented by aplyronines, have been isolated from sea hares in Japanese waters. Although earlier studies indicated the potent antitumor activity of aplyronines, their clinical development has never been conducted because of the minute amount of compound available from the natural source. Recent synthetic studies, however, have made it possible to prepare these compounds and analogs for a structure-activity relationship study, and started to uncover their unique action mechanism towards their putative targets, microfilaments. Here, recent findings of small antitumor molecules isolated from Japanese sea hares are reviewed. Sea hares are also known to produce cytotoxic and antimicrobial proteins. In contrast to the small molecules of dietary origin, proteins are the genetic products of sea hares and they are likely to have some primary physiological functions in addition to ecological roles in the sea hare. Based on the biochemical properties and phylogenetic analysis of these proteins, we propose that they belong to one family of molecule, the "Aplysianin A family," although their molecular weights are apparently divided into two groups. Interestingly, the active principles in Aplysia species and Dolabella auricularia were shown to be L-amino acid oxidase (LAAO), a flavin enzyme that oxidizes an alpha-amino group of the substrate with

  10. Tuberculosis Therapy Modifies the Cytokine Profile, Maturation State, and Expression of Inhibitory Molecules on Mycobacterium tuberculosis-Specific CD4+ T-Cells

    PubMed Central

    Saharia, Kapil K.; Petrovas, Constantinos; Ferrando-Martinez, Sara; Leal, Manuel; Luque, Rafael; Ive, Prudence; Luetkemeyer, Anne; Havlir, Diane; Koup, Richard A.

    2016-01-01

    Background Little is known about the expression of inhibitory molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed-death-1 (PD-1) on Mycobacterium tuberculosis (Mtb)-specific CD4 T-cells and how their expression is impacted by TB treatment. Methods Cryopreserved PBMCs from HIV-TB co-infected and TB mono-infected patients with untreated and treated tuberculosis (TB) disease were stimulated for six hours with PPD and stained. Using polychromatic flow cytometry, we characterized the differentiation state, cytokine profile, and inhibitory molecule expression on PPD-specific CD4 T-cells. Results In our HIV-TB co-infected cohort, TB treatment increased the proportion of PPD-specific CD4 T-cells co-producing IFN-γ+IL-2+TNF-α+ and IFN-γ+IL-2+ (p = 0.0004 and p = 0.0002, respectively) while decreasing the proportion of PPD-specific CD4 T-cells co-producing IFN-γ+MIP1-β+TNF-α+ and IFN-γ+MIP1-β+. The proportion of PPD-specific CD4 T-cells expressing an effector memory phenotype decreased (63.6% vs 51.6%, p = 0.0015) while the proportion expressing a central memory phenotype increased (7.8% vs. 21.7%, p = 0.001) following TB treatment. TB treatment reduced the proportion of PPD-specific CD4 T-cells expressing CTLA-4 (72.4% vs. 44.3%, p = 0.0005) and PD-1 (34.5% vs. 29.2%, p = 0.03). Similar trends were noted in our TB mono-infected cohort. Conclusion TB treatment alters the functional profile of Mtb-specific CD4 T-cells reflecting shifts towards a less differentiated maturational profile and decreases PD-1 and CTLA-4 expression. These could serve as markers of reduced mycobacterial burden. Further study is warranted. PMID:27367521

  11. Simple molecules as complex systems.

    PubMed

    Furtenbacher, Tibor; Arendás, Péter; Mellau, Georg; Császár, Attila G

    2014-01-01

    For individual molecules quantum mechanics (QM) offers a simple, natural and elegant way to build large-scale complex networks: quantized energy levels are the nodes, allowed transitions among the levels are the links, and transition intensities supply the weights. QM networks are intrinsic properties of molecules and they are characterized experimentally via spectroscopy; thus, realizations of QM networks are called spectroscopic networks (SN). As demonstrated for the rovibrational states of H2(16)O, the molecule governing the greenhouse effect on earth through hundreds of millions of its spectroscopic transitions (links), both the measured and first-principles computed one-photon absorption SNs containing experimentally accessible transitions appear to have heavy-tailed degree distributions. The proposed novel view of high-resolution spectroscopy and the observed degree distributions have important implications: appearance of a core of highly interconnected hubs among the nodes, a generally disassortative connection preference, considerable robustness and error tolerance, and an "ultra-small-world" property. The network-theoretical view of spectroscopy offers a data reduction facility via a minimum-weight spanning tree approach, which can assist high-resolution spectroscopists to improve the efficiency of the assignment of their measured spectra. PMID:24722221

  12. Molecules in the early universe

    SciTech Connect

    Lepp, S.; Shull, J.M.

    1984-05-15

    We present calculations of the formation of astrophysically interesting molecules (H/sub 2/, HD, LiH, and HeH/sup +/) by gas-phase reactions during the postrecombination epoch (redshifts z = 300-30). In standard Friedmann cosmological models, H/sub 2//Hroughly-equal10/sup -6/, HD/H/sub 2/roughly-equal10/sup -4.5/, and LiH/H/sub 2/roughly-equal10/sup -6.5/. These molecules may dominate the cooling and trigger the collapse of primordial gas clouds. The dipole rotational transitions of HD and LiH are particularly important at high density and low temperature. Additional molecules form during spherical collapse of these clouds, their rotational cooling keeps the gas temperature between 400 and 1500 K over 12 decades of density increase until the H/sub 2/ lines become optically thick. The existence of molecular coolants at high redshift has significant implications for the first generation of stars and for thermal instabilities in intergalactic matter.

  13. Simple molecules as complex systems

    PubMed Central

    Furtenbacher, Tibor; Árendás, Péter; Mellau, Georg; Császár, Attila G.

    2014-01-01

    For individual molecules quantum mechanics (QM) offers a simple, natural and elegant way to build large-scale complex networks: quantized energy levels are the nodes, allowed transitions among the levels are the links, and transition intensities supply the weights. QM networks are intrinsic properties of molecules and they are characterized experimentally via spectroscopy; thus, realizations of QM networks are called spectroscopic networks (SN). As demonstrated for the rovibrational states of H216O, the molecule governing the greenhouse effect on earth through hundreds of millions of its spectroscopic transitions (links), both the measured and first-principles computed one-photon absorption SNs containing experimentally accessible transitions appear to have heavy-tailed degree distributions. The proposed novel view of high-resolution spectroscopy and the observed degree distributions have important implications: appearance of a core of highly interconnected hubs among the nodes, a generally disassortative connection preference, considerable robustness and error tolerance, and an “ultra-small-world” property. The network-theoretical view of spectroscopy offers a data reduction facility via a minimum-weight spanning tree approach, which can assist high-resolution spectroscopists to improve the efficiency of the assignment of their measured spectra. PMID:24722221

  14. A single-molecule diode

    PubMed Central

    Elbing, Mark; Ochs, Rolf; Koentopp, Max; Fischer, Matthias; von Hänisch, Carsten; Weigend, Florian; Evers, Ferdinand; Weber, Heiko B.; Mayor, Marcel

    2005-01-01

    We have designed and synthesized a molecular rod that consists of two weakly coupled electronic π -systems with mutually shifted energy levels. The asymmetry thus implied manifests itself in a current–voltage characteristic with pronounced dependence on the sign of the bias voltage, which makes the molecule a prototype for a molecular diode. The individual molecules were immobilized by sulfur–gold bonds between both electrodes of a mechanically controlled break junction, and their electronic transport properties have been investigated. The results indeed show diode-like current–voltage characteristics. In contrast to that, control experiments with symmetric molecular rods consisting of two identical π -systems did not show significant asymmetries in the transport properties. To investigate the underlying transport mechanism, phenomenological arguments are combined with calculations based on density functional theory. The theoretical analysis suggests that the bias dependence of the polarizability of the molecule feeds back into the current leading to an asymmetric shape of the current–voltage characteristics, similar to the phenomena in a semiconductor diode. PMID:15956208

  15. Functional molecules in electronic circuits.

    PubMed

    Weibel, Nicolas; Grunder, Sergio; Mayor, Marcel

    2007-08-01

    Molecular electronics is a fascinating field of research contributing to both fundamental science and future technological achievements. A promising starting point for molecular devices is to mimic existing electronic functions to investigate the potential of molecules to enrich and complement existing electronic strategies. Molecules designed and synthesized to be integrated into electronic circuits and to perform an electronic function are presented in this article. The focus is set in particular on rectification and switching based on molecular devices, since the control over these two parameters enables the assembly of memory units, likely the most interesting and economic application of molecular based electronics. Both historical and contemporary solutions to molecular rectification are discussed, although not exhaustively. Several examples of integrated molecular switches that respond to light are presented. Molecular switches responding to an electrochemical signal are also discussed. Finally, supramolecular and molecular systems with intuitive application potential as memory units due to their hysteretic switching are highlighted. Although a particularly attractive feature of molecular electronics is its close cooperation with neighbouring disciplines, this article is written from the point of view of a chemist. Although the focus here is largely on molecular considerations, innovative contributions from physics, electro engineering, nanotechnology and other scientific disciplines are equally important. However, the ability of the chemist to correlate function with structure, to design and to provide tailor-made functional molecules is central to molecular electronics. PMID:17637951

  16. Water molecules orientation in surface layer

    NASA Astrophysics Data System (ADS)

    Klingo, V. V.

    2000-08-01

    The water molecules orientation has been investigated theoretically in the water surface layer. The surface molecule orientation is determined by the direction of a molecule dipole moment in relation to outward normal to the water surface. Entropy expressions of the superficial molecules in statistical meaning and from thermodynamical approach to a liquid surface tension have been found. The molecules share directed opposite to the outward normal that is hydrogen protons inside is equal 51.6%. 48.4% water molecules are directed along to surface outward normal that is by oxygen inside. A potential jump at the water surface layer amounts about 0.2 volts.

  17. Interplay between magnetic anisotropy and vibron-assisted tunneling in a single-molecule magnet transistor

    NASA Astrophysics Data System (ADS)

    Park, Kyungwha; McCaskey, Alexander; Yamamoto, Yoh; Warnock, Michael; Burzuri, Enrique; van der Zant, Herre

    2015-03-01

    Molecules trapped in single-molecule devices vibrate with discrete frequencies characteristic to the molecules, and the molecular vibrations can couple to electronic charge and/or spin degrees of freedom. For a significant electron-vibron coupling, electrons may tunnel via the vibrational excitations unique to the molecules. Recently, electron transport via individual anisotropic magnetic molecules (referred to as single-molecule magnets) has been observed in single-molecule transistors. A single-molecule magnet has a large spin moment and a large magnetic anisotropy barrier. So far, studies of electron-vibron coupling effects in single-molecule devices, are mainly for isotropic molecules. Here we investigate how the electron-vibron coupling influences electron transport via a single-molecule magnet Fe4, by using a model Hamiltonian with parameter values obtained from density-functional theory (arXiv:1411.2677). We show that the magnetic anisotropy of the Fe4 induces new features in vibrational conductance peaks and creates vibrational satellite peaks. The main and satellite peak heights have a strong, unusual dependence on the direction and magnitude of applied magnetic field, because the magnetic anisotropy barrier is comparable to vibrational energies. Funding from NSF DMR-1206354, EU FP7 program project 618082 ACMOL, advanced ERC grant (Mols@Mols). Computer resources from SDSC Trestles under DMR060009N and VT ARC.

  18. DUO: Spectra of diatomic molecules

    NASA Astrophysics Data System (ADS)

    Yurchenko, Sergei N.; Lodi, Lorenzo; Tennyson, Jonathan; Stolyarov, Andrey V.

    2016-05-01

    Duo computes rotational, rovibrational and rovibronic spectra of diatomic molecules. The software, written in Fortran 2003, solves the Schrödinger equation for the motion of the nuclei for the simple case of uncoupled, isolated electronic states and also for the general case of an arbitrary number and type of couplings between electronic states. Possible couplings include spin–orbit, angular momenta, spin-rotational and spin–spin. Introducing the relevant couplings using so-called Born–Oppenheimer breakdown curves can correct non-adiabatic effects.

  19. XUV ionization of aligned molecules

    SciTech Connect

    Kelkensberg, F.; Siu, W.; Gademann, G.; Rouzee, A.; Vrakking, M. J. J.; Johnsson, P.; Lucchini, M.; Lucchese, R. R.

    2011-11-15

    New extreme-ultraviolet (XUV) light sources such as high-order-harmonic generation (HHG) and free-electron lasers (FELs), combined with laser-induced alignment techniques, enable novel methods for making molecular movies based on measuring molecular frame photoelectron angular distributions. Experiments are presented where CO{sub 2} molecules were impulsively aligned using a near-infrared laser and ionized using femtosecond XUV pulses obtained by HHG. Measured electron angular distributions reveal contributions from four orbitals and the onset of the influence of the molecular structure.

  20. Nanoelectronics of a DNA molecule

    NASA Astrophysics Data System (ADS)

    Albuquerque, E. L.; Fulco, U. L.; Caetano, E. W. S.; Freire, V. N.; Lyra, M. L.; Moura, F. A. B. F.

    2014-03-01

    We investigate the nanoelectronic properties of a double-strand quasiperiodic DNA molecule, modeled by a tight-binding effective Hamiltonian, which includes contributions from the nucleobasis system as well as the sugar-phosphate backbone. Our theoretical approach makes use of Dyson's equation together with a transfer-matrix treatment, to investigate the electronic density of states, the electronic transmissivity, and the current-voltage characteristic curves of sequences of a DNA finite segment.We compared the electronic transport found for the quasiperiodic structure to those using a sequence of natural DNA, as part of the human chromosome Ch22.

  1. Advancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes.

    PubMed

    Schreiber, Stuart L; Kotz, Joanne D; Li, Min; Aubé, Jeffrey; Austin, Christopher P; Reed, John C; Rosen, Hugh; White, E Lucile; Sklar, Larry A; Lindsley, Craig W; Alexander, Benjamin R; Bittker, Joshua A; Clemons, Paul A; de Souza, Andrea; Foley, Michael A; Palmer, Michelle; Shamji, Alykhan F; Wawer, Mathias J; McManus, Owen; Wu, Meng; Zou, Beiyan; Yu, Haibo; Golden, Jennifer E; Schoenen, Frank J; Simeonov, Anton; Jadhav, Ajit; Jackson, Michael R; Pinkerton, Anthony B; Chung, Thomas D Y; Griffin, Patrick R; Cravatt, Benjamin F; Hodder, Peter S; Roush, William R; Roberts, Edward; Chung, Dong-Hoon; Jonsson, Colleen B; Noah, James W; Severson, William E; Ananthan, Subramaniam; Edwards, Bruce; Oprea, Tudor I; Conn, P Jeffrey; Hopkins, Corey R; Wood, Michael R; Stauffer, Shaun R; Emmitte, Kyle A

    2015-06-01

    Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the NIH launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines but also highlight the need to innovate the science of therapeutic discovery. PMID:26046436

  2. Hydrophobic Porous Material Adsorbs Small Organic Molecules

    NASA Technical Reports Server (NTRS)

    Sharma, Pramod K.; Hickey, Gregory S.

    1994-01-01

    Composite molecular-sieve material has pore structure designed specifically for preferential adsorption of organic molecules for sizes ranging from 3 to 6 angstrom. Design based on principle that contaminant molecules become strongly bound to surface of adsorbent when size of contaminant molecules is nearly same as that of pores in adsorbent. Material used to remove small organic contaminant molecules from vacuum systems or from enclosed gaseous environments like closed-loop life-support systems.

  3. Spin squeezing a cold molecule

    NASA Astrophysics Data System (ADS)

    Bhattacharya, M.

    2015-12-01

    In this article we present a concrete proposal for spin squeezing the cold ground-state polar paramagnetic molecule OH, a system currently under fine control in the laboratory. In contrast to existing work, we consider a single, noninteracting molecule with angular momentum greater than 1 /2 . Starting from an experimentally relevant effective Hamiltonian, we identify an adiabatic regime where different combinations of static electric and magnetic fields can be used to realize the single-axis twisting Hamiltonian of Kitagawa and Ueda [M. Kitagawa and M. Ueda, Phys. Rev. A 47, 5138 (1993), 10.1103/PhysRevA.47.5138], the uniform field Hamiltonian proposed by Law et al. [C. K. Law, H. T. Ng, and P. T. Leung, Phys. Rev. A 63, 055601 (2001), 10.1103/PhysRevA.63.055601], and a model of field propagation in a Kerr medium considered by Agarwal and Puri [G. S. Agarwal and R. R. Puri, Phys. Rev. A 39, 2969 (1989), 10.1103/PhysRevA.39.2969]. We then consider the situation in which nonadiabatic effects are quite large and show that the effective Hamiltonian supports spin squeezing even in this case. We provide analytical expressions as well as numerical calculations, including optimization of field strengths and accounting for the effects of field misalignment. Our results have consequences for applications such as precision spectroscopy, techniques such as magnetometry, and stereochemical effects such as the orientation-to-alignment transition.

  4. Electronic spectroscopy of diatomic molecules

    NASA Technical Reports Server (NTRS)

    Partridge, Harry; Langhoff, Stephen R.; Bauschlicher, Charles W., Jr.

    1994-01-01

    This article provides an overview of the principal computational approaches and their accuracy for the study of electronic spectroscopy of diatomic molecules. We include a number of examples from our work that illustrate the range of application. We show how full configuration interaction benchmark calculations were instrumental in improving the understanding of the computational requirements for obtaining accurate results for diatomic spectroscopy. With this understanding it is now possible to compute radiative lifetimes accurate to within 10% for systems involving first- and second-row atoms. We consider the determination of the infrared vibrational transition probabilities for the ground states of SiO and NO, based on a globally accurate dipole moment function. We show how we were able to assign the a(sup "5)II state of CO as the upper state in the recently observed emission bands of CO in an Ar matrix. We next discuss the assignment of the photoelectron detachment spectra of NO and the alkali oxide negative ions. We then present several examples illustrating the state-of-the-art in determining radiative lifetimes for valence-valence and valence-Rydberg transitions. We next compare the molecular spectroscopy of the valence isoelectronic B2, Al2, and AlB molecules. The final examples consider systems involving transition metal atoms, which illustrate the difficulty in describing states with different numbers of d electrons.

  5. Characterization of Interstellar Organic Molecules

    SciTech Connect

    Gencaga, Deniz; Knuth, Kevin H.; Carbon, Duane F.

    2008-11-06

    Understanding the origins of life has been one of the greatest dreams throughout history. It is now known that star-forming regions contain complex organic molecules, known as Polycyclic Aromatic Hydrocarbons (PAHs), each of which has particular infrared spectral characteristics. By understanding which PAH species are found in specific star-forming regions, we can better understand the biochemistry that takes place in interstellar clouds. Identifying and classifying PAHs is not an easy task: we can only observe a single superposition of PAH spectra at any given astrophysical site, with the PAH species perhaps numbering in the hundreds or even thousands. This is a challenging source separation problem since we have only one observation composed of numerous mixed sources. However, it is made easier with the help of a library of hundreds of PAH spectra. In order to separate PAH molecules from their mixture, we need to identify the specific species and their unique concentrations that would provide the given mixture. We develop a Bayesian approach for this problem where sources are separated from their mixture by Metropolis Hastings algorithm. Separated PAH concentrations are provided with their error bars, illustrating the uncertainties involved in the estimation process. The approach is demonstrated on synthetic spectral mixtures using spectral resolutions from the Infrared Space Observatory (ISO). Performance of the method is tested for different noise levels.

  6. Time scales for molecule formation by ion-molecule reactions

    NASA Technical Reports Server (NTRS)

    Langer, W. D.; Glassgold, A. E.

    1976-01-01

    Analytical solutions are obtained for nonlinear differential equations governing the time-dependence of molecular abundances in interstellar clouds. Three gas-phase reaction schemes are considered separately for the regions where each dominates. The particular case of CO, and closely related members of the Oh and CH families of molecules, is studied for given values of temperature, density, and the radiation field. Nonlinear effects and couplings with particular ions are found to be important. The time scales for CO formation range from 100,000 to a few million years, depending on the chemistry and regime. The time required for essentially complete conversion of C(+) to CO in the region where the H3(+) chemistry dominates is several million years. Because this time is longer than or comparable to dynamical time scales for dense interstellar clouds, steady-state abundances may not be observed in such clouds.

  7. Ultrafast electron diffraction from aligned molecules

    SciTech Connect

    Centurion, Martin

    2015-08-17

    The aim of this project was to record time-resolved electron diffraction patterns of aligned molecules and to reconstruct the 3D molecular structure. The molecules are aligned non-adiabatically using a femtosecond laser pulse. A femtosecond electron pulse then records a diffraction pattern while the molecules are aligned. The diffraction patterns are then be processed to obtain the molecular structure.

  8. Mechanical studies on single molecules: general considerations

    NASA Astrophysics Data System (ADS)

    Bensimon, David; Croquette, Vincent

    2015-10-01

    The following sections are included: * Elements of molecular biology * Advantages and drawbacks of single molecule studies * Order of magnitude of the relevant parameters at the single molecule level * Single molecule manipulation techniques * Comparison of the different techniques * DNA mechanical properties * Conclusion * Bibliography

  9. Nanometer Resolution Imaging by SIngle Molecule Switching

    SciTech Connect

    Hu, Dehong; Orr, Galya

    2010-04-02

    The fluorescence intensity of single molecules can change dramatically even under constant laser excitation. The phenomenon is frequently called "blinking" and involves molecules switching between high and low intensity states.[1-3] In additional to spontaneous blinking, the fluorescence of some special fluorophores, such as cyanine dyes and photoactivatable fluorescent proteins, can be switched on and off by choice using a second laser. Recent single-molecule spectroscopy investigations have shed light on mechanisms of single molecule blinking and photoswitching. This ability to controllably switch single molecules led to the invention of a novel fluorescence microscopy with nanometer spatial resolution well beyond the diffraction limit.

  10. Electrokinetic concentration of charged molecules

    DOEpatents

    Singh, Anup K.; Neyer, David W.; Schoeniger, Joseph S.; Garguilo, Michael G.

    2002-01-01

    A method for separating and concentrating charged species from uncharged or neutral species regardless of size differential. The method uses reversible electric field induced retention of charged species, that can include molecules and molecular aggregates such as dimers, polymers, multimers, colloids, micelles, and liposomes, in volumes and on surfaces of porous materials. The retained charged species are subsequently quantitatively removed from the porous material by a pressure driven flow that passes through the retention volume and is independent of direction thus, a multi-directional flow field is not required. Uncharged species pass through the system unimpeded thus effecting a complete separation of charged and uncharged species and making possible concentration factors greater than 1000-fold.

  11. Photoluminescence of a Plasmonic Molecule.

    PubMed

    Huang, Da; Byers, Chad P; Wang, Lin-Yung; Hoggard, Anneli; Hoener, Ben; Dominguez-Medina, Sergio; Chen, Sishan; Chang, Wei-Shun; Landes, Christy F; Link, Stephan

    2015-07-28

    Photoluminescent Au nanoparticles are appealing for biosensing and bioimaging applications because of their non-photobleaching and non-photoblinking emission. The mechanism of one-photon photoluminescence from plasmonic nanostructures is still heavily debated though. Here, we report on the one-photon photoluminescence of strongly coupled 50 nm Au nanosphere dimers, the simplest plasmonic molecule. We observe emission from coupled plasmonic modes as revealed by single-particle photoluminescence spectra in comparison to correlated dark-field scattering spectroscopy. The photoluminescence quantum yield of the dimers is found to be surprisingly similar to the constituent monomers, suggesting that the increased local electric field of the dimer plays a minor role, in contradiction to several proposed mechanisms. Aided by electromagnetic simulations of scattering and absorption spectra, we conclude that our data are instead consistent with a multistep mechanism that involves the emission due to radiative decay of surface plasmons generated from excited electron-hole pairs following interband absorption. PMID:26165983

  12. Diamond Molecules Found in Petroleum

    NASA Astrophysics Data System (ADS)

    Carlson, R. M. K.; Dahl, J. E. P.; Liu, S. G.; Olmstead, M. M.; Buerki, P. R.; Gat, R.

    We recently reported [1,2] the discovery and isolation of new members of the hydrogen-terminated diamond series, ˜1 to ˜2 nm sized higher diamondoids from petroleum. Crystallographic studies [1,2] revealed a wealth of diamond molecules that are nanometer-sized rods, helices, discs, pyramids, etc. Highly rigid, well-defined, readily derivatizable structures make them valuable molecular building blocks for nanotechnology. We now produce certain higher diamondoids in gram quantities. Although more stable than graphite particles of comparable size, higher diamondoids are extraordinarily difficult to synthesize. Attempts to synthesize them were abandoned in the 1980's. We examined extracts of diamond-containing materials synthesized by CO2 laser-induced gas-phase synthesis [3] and commercial CVD in an attempt to detect diamantane to undecamantane. However, high-sensitivity GCMS detected no diamondoids in these materials.

  13. Nonadiabatic calculations on hydrogen molecule

    NASA Astrophysics Data System (ADS)

    Komasa, Jacek; Pachucki, Krzysztof

    Since its infancy quantum mechanics has treated hydrogen molecule as a test bed. Contemporary spectroscopy is able to supply the dissociation energy (D0) of H2 with the accuracy of 3 . 7 .10-4cm-1 , while current theoretical predictions are 10-3cm-1 in error. Both the uncertainties are already smaller than the quantum electrodynamic (QED) effects contributing to D0, which poses a particular challenge to theoreticians. Undoubtedly, in order to increase the predictive power of theory one has to not only account for the multitude of the tiny relativistic and QED effects but, especially, significantly increase precision of the largest component of D0--the nonrelativistic contribution. We approach the problem of solving the Schroedinger equation, equipped with new methodology, with the target precision of D0 set at the level of 10-7cm-1 .

  14. New molecules for hippocampal development.

    PubMed

    Skutella, T; Nitsch, R

    2001-02-01

    Pathfinding by developing axons towards their proper targets is an essential step in establishing appropriate neuronal connections. Recent work involving cell culture assays and molecular biology strategies, including knockout animals, strongly indicates that a complex network of guidance signals regulates the formation of hippocampal connections during development. Outgrowing axons are routed towards the hippocampal formation by specific expression of long-range cues, which include secreted class 3 semaphorins, netrin 1 and Slit proteins. Local membrane- or substrate-anchored molecules, such as ligands of the ephrin A subclass, provide layer-specific positional information. Understanding the molecular mechanisms that underlie axonal guidance during hippocampal development might be of importance in making therapeutic use of sprouting fibers, which are produced following the loss of afferents in CNS lesion. PMID:11164941

  15. Energy transfer mechanisms between molecules

    NASA Technical Reports Server (NTRS)

    Meador, W. E.

    1985-01-01

    Reliable rate coefficients for energy transfer and relaxation phenomena are needed in order to do the theoretical modeling which is necessary for accomplishing the following objectives: understanding and justifying proposed laser systems, determining limitations, identifying control parameters, and scaling to space-power requirements. Modeling also establishes the criteria to be followed for lasant selection. Lack of knowledge of rate coefficients is invariably the biggest obstacle to successful modeling. Existing theoretical methods are discussed, sources of error are identified, and transfer laser criteria suggested by the theory are listed. The emphasis is on vibrational-vibrational (V-V) energy transfer caused by both short range and long range interactions between molecules. Special attention is given to the importance of near-resonant collisional and dipole-dipole transfer. A technique is proposed for significantly improving the theoretical predictions of rate coefficients.

  16. Electrorheological crystallization of proteins and other molecules

    DOEpatents

    Craig, G.D.; Rupp, B.

    1996-06-11

    An electrorheological crystalline mass of a molecule is formed by dispersing the molecule in a dispersion fluid and subjecting the molecule dispersion to a uniform electrical field for a period of time during which time an electrorheological crystalline mass is formed. Molecules that may be used to form an electrorheological crystalline mass include any organic or inorganic molecule which has a permanent dipole and/or which is capable of becoming an induced dipole in the presence of an electric field. The molecules used to form the electrorheological crystalline mass are preferably macromolecules, such as biomolecules, such as proteins, nucleic acids, carbohydrates, lipoproteins and viruses. Molecules are crystallized by a method in which an electric field is maintained for a period of time after the electrorheological crystalline mass has formed during which time at least some of the molecules making up the electrorheological crystalline mass form a crystal lattice. The three dimensional structure of a molecule is determined by a method in which an electrorheological crystalline mass of the molecule is formed, an X-ray diffraction pattern of the electrorheological crystalline mass is obtained and the three dimensional structure of the molecule is calculated from the X-ray diffraction pattern. 4 figs.

  17. Electrorheological crystallization of proteins and other molecules

    DOEpatents

    Craig, George D.; Rupp, Bernhard

    1996-01-01

    An electrorheological crystalline mass of a molecule is formed by dispersing the molecule in a dispersion fluid and subjecting the molecule dispersion to a uniform electrical field for a period of time during which time an electrorheological crystalline mass is formed. Molecules that may be used to form an electrorheological crystalline mass include any organic or inorganic molecule which has a permanent dipole and/or which is capable of becoming an induced dipole in the presence of an electric field. The molecules used to form the electrorheological crystalline mass are preferably macromolecules, such as biomolecules, such as proteins, nucleic acids, carbohydrates, lipoproteins and viruses. Molecules are crystallized by a method in which an electric field is maintained for a period of time after the electrorheological crystalline mass has formed during which time at least some of the molecules making up the electrorheological crystalline mass form a crystal lattice. The three dimensional structure of a molecule is determined by a method in which an electrorheological crystalline mass of the molecule is formed, an x-ray diffraction pattern of the electrorheological crystalline mass is obtained and the three dimensional structure of the molecule is calculated from the x-ray diffraction pattern.

  18. Deformation of DNA molecules by hydrodynamic focusing

    NASA Astrophysics Data System (ADS)

    Wong, Pak Kin; Lee, Yi-Kuen; Ho, Chih-Ming

    2003-12-01

    The motion of a DNA molecule in a solvent flow reflects the deformation of a nano/microscale flexible mass spring structure by the forces exerted by the fluid molecules. The dynamics of individual molecules can reveal both fundamental properties of the DNA and basic understanding of the complex rheological properties of long-chain molecules. In this study, we report the dynamics of isolated DNA molecules under homogeneous extensional flow. Hydrodynamic focusing generates homogeneous extensional flow with uniform velocity in the transverse direction. The deformation of individual DNA molecules in the flow was visualized with video fluorescence microscopy. A coil stretch transition was observed when the Deborah number (De) is larger than 0.8. With a sudden stopping of the flow, the DNA molecule relaxes and recoils. The longest relaxation time of T2 DNA was determined to be 0.63 s when scaling viscosity to 0.9 cP.

  19. Single-molecule imaging by optical absorption

    NASA Astrophysics Data System (ADS)

    Celebrano, Michele; Kukura, Philipp; Renn, Alois; Sandoghdar, Vahid

    2011-02-01

    To date, optical studies of single molecules at room temperature have relied on the use of materials with high fluorescence quantum yield combined with efficient spectral rejection of background light. To extend single-molecule studies to a much larger pallet of substances that absorb but do not fluoresce, scientists have explored the photothermal effect, interferometry, direct attenuation and stimulated emission. Indeed, very recently, three groups have succeeded in achieving single-molecule sensitivity in absorption. Here, we apply modulation-free transmission measurements known from absorption spectrometers to image single molecules under ambient conditions both in the emissive and strongly quenched states. We arrive at quantitative values for the absorption cross-section of single molecules at different wavelengths and thereby set the ground for single-molecule absorption spectroscopy. Our work has important implications for research ranging from absorption and infrared spectroscopy to sensing of unlabelled proteins at the single-molecule level.

  20. Quantum Monte Carlo studies on small molecules

    NASA Astrophysics Data System (ADS)

    Galek, Peter T. A.; Handy, Nicholas C.; Lester, William A., Jr.

    The Variational Monte Carlo (VMC) and Fixed-Node Diffusion Monte Carlo (FNDMC) methods have been examined, through studies on small molecules. New programs have been written which implement the (by now) standard algorithms for VMC and FNDMC. We have employed and investigated throughout our studies the accuracy of the common Slater-Jastrow trial wave function. Firstly, we have studied a range of sizes of the Jastrow correlation function of the Boys-Handy form, obtained using our optimization program with analytical derivatives of the central moments in the local energy. Secondly, we have studied the effects of Slater-type orbitals (STOs) that display the exact cusp behaviour at nuclei. The orbitals make up the all important trial determinant, which determines the fixed nodal surface. We report all-electron calculations for the ground state energies of Li2, Be2, H2O, NH3, CH4 and H2CO, in all cases but one with accuracy in excess of 95%. Finally, we report an investigation of the ground state energies, dissociation energies and ionization potentials of NH and NH+. Recent focus paid in the literature to these species allow for an extensive comparison with other ab initio methods. We obtain accurate properties for the species and reveal a favourable tendency for fixed-node and other systematic errors to cancel. As a result of our accurate predictions, we are able to obtain a value for the heat of formation of NH, which agrees to within less than 1 kcal mol-1 to other ab initio techniques and 0.2 kcal mol-1 of the experimental value.

  1. PREFACE: Processes in Isotopes and Molecules

    NASA Astrophysics Data System (ADS)

    Bogdan, Diana; Tosa, Valer

    2009-07-01

    These Proceedings present some of the Invited Lectures and Contributed Papers of the International Conference 'Processes in Isotopes and Molecules' (PIM), held in Cluj-Napoca, Romania, 24-26 September 2009. The PIM conference, started in 1999 as a local event, is now an international conference organized every two years by the National Institute for R&D of Isotopic and Molecular Technologies in Cluj-Napoca, the capital city of Transylvania, Romania. The meetings are attended by researchers in the field of atomic and molecular physics as well as those developing new materials and technologies. The scientific subjects are at the cross-roads of three fundamental research areas: physics, chemistry, and biology. The papers here are grouped according to the five conference topics: T1 - Molecular and biomolecular systems T2 - Modern techniques and technologies T3 - Environmental molecular processes T4 - Hydrogen and renewable sources of energy T5 - Nanostructured materials and nanocomposites We gratefully acknowledge the contribution of our colleagues from the Scientific Committee and Program Committee who contributed their time, energy and expertise to the refereeing process. Finally, we would like to thank people from IOP Publishing for their friendly advice and prompt help during the editing process, as well as for their efforts making the Journal of Physics: Conference Series available to the scientific community. Diana Bogdan and Valer Tosa National Institute for R&D Isotopic and Molecular Technologies, Cluj-Napoca

  2. Small-molecule caspase inhibitors

    NASA Astrophysics Data System (ADS)

    Zhenodarova, S. M.

    2010-02-01

    The review considers low-molecular weight inhibitors of caspases, cysteine proteases being key contributors to apoptosis (programmed cell death). The inhibitors with aspartic acid residues or various heterocyclic systems (both synthetic and natural) are covered. Their possible mechanisms of action are discussed. Data on inhibitor structure-activity relationship studies are systematically surveyed. The interactions of the non-peptide fragments of an inhibitor with the enzymes are examined. Examples of the use of some inhibitors for apoptosis suppression are provided.

  3. Geochemical Origin of Biological Molecules

    NASA Astrophysics Data System (ADS)

    Bassez, Marie-Paule

    2013-04-01

    A model for the geochemical origin of biological molecules is presented. Rocks such as peridotites and basalts, which contain ferromagnesian minerals, evolve in the presence of water. Their hydrolysis is an exothermic reaction which generates heat and a release of H2 and of minerals with modified structures. The hydrogen reacts with the CO2 embedded inside the rock or with the CO2 of the environment to form CO in an hydrothermal process. With the N2 of the environment, and with an activation source arising from cosmic radiation, ferromagnesian rocks might evolve towards the abiotic formation of biological molecules, such as peptide like macromolecules which produce amino acids after acid hydrolysis. The reactions concerned are described. The production of hydrothermal CO is discussed in geological sites containing ferromagnesian silicate minerals and the low intensity of the Earth's magnetic field during Paleoarchaean Era is also discussed. It is concluded that excitation sources arising from cosmic radiation were much more abundant during Paleoarchaean Era and that macromolecular structures of biological relevance might consequently form during Archaean Eon, as a product of the chemical evolution of the rocks and of their mineral contents. This synthesis of abiotically formed biological molecules is consecutively discussed for meteorites and other planets such as Mars. This model for the geochemical origin of biological molecules has first been proposed in 2008 in the context of reactions involving catalysers such as kaolinite [Bassez 2008a] and then presented in conferences and articles [Bassez 2008b, 2009, 2012; Bassez et al. 2009a to 2012b]. BASSEZ M.P. 2008a Synthèse prébiotique dans les conditions hydrothermales, CNRIUT'08, Lyon 29-30/05/2008, Conf. and open access article:http://liris.cnrs.fr/~cnriut08/actes/ 29 mai 11h-12h40. BASSEZ M.P. 2008b Prebiotic synthesis under hydrothermal conditions, ISSOL'08, P2-6, Firenze-Italy, 24-29/08/2008. Poster at the

  4. NMR studies of oriented molecules

    SciTech Connect

    Sinton, S.W.

    1981-11-01

    Deuterium and proton magnetic resonance are used in experiments on a number of compounds which either form liquid crystal mesophases themselves or are dissolved in a liquid crystal solvent. Proton multiple quantum NMR is used to simplify complicated spectra. The theory of nonselective multiple quantum NMR is briefly reviewed. Benzene dissolved in a liquid crystal are used to demonstrate several outcomes of the theory. Experimental studies include proton and deuterium single quantum (..delta..M = +-1) and proton multiple quantum spectra of several molecules which contain the biphenyl moiety. 4-Cyano-4'-n-pentyl-d/sub 11/-biphenyl (5CB-d/sub 11/) is studied as a pure compound in the nematic phase. The obtained chain order parameters and dipolar couplings agree closely with previous results. Models for the effective symmetry of the biphenyl group in 5CB-d/sub 11/ are tested against the experimental spectra. The dihedral angle, defined by the planes containing the rings of the biphenyl group, is found to be 30 +- 2/sup 0/ for 5DB-d/sub 11/. Experiments are also described for 4,4'-d/sub 2/-biphenyl, 4,4' - dibromo-biphenyl, and unsubstituted biphenyl.

  5. Single Molecule Studies of Chromatin

    SciTech Connect

    Jeans, C; Thelen, M P; Noy, A

    2006-02-06

    In eukaryotic cells, DNA is packaged as chromatin, a highly ordered structure formed through the wrapping of the DNA around histone proteins, and further packed through interactions with a number of other proteins. In order for processes such as DNA replication, DNA repair, and transcription to occur, the structure of chromatin must be remodeled such that the necessary enzymes can access the DNA. A number of remodeling enzymes have been described, but our understanding of the remodeling process is hindered by a lack of knowledge of the fine structure of chromatin, and how this structure is modulated in the living cell. We have carried out single molecule experiments using atomic force microscopy (AFM) to study the packaging arrangements in chromatin from a variety of cell types. Comparison of the structures observed reveals differences which can be explained in terms of the cell type and its transcriptional activity. During the course of this project, sample preparation and AFM techniques were developed and optimized. Several opportunities for follow-up work are outlined which could provide further insight into the dynamic structural rearrangements of chromatin.

  6. Broadband single-molecule excitation spectroscopy

    PubMed Central

    Piatkowski, Lukasz; Gellings, Esther; van Hulst, Niek F.

    2016-01-01

    Over the past 25 years, single-molecule spectroscopy has developed into a widely used tool in multiple disciplines of science. The diversity of routinely recorded emission spectra does underpin the strength of the single-molecule approach in resolving the heterogeneity and dynamics, otherwise hidden in the ensemble. In early cryogenic studies single molecules were identified by their distinct excitation spectra, yet measuring excitation spectra at room temperature remains challenging. Here we present a broadband Fourier approach that allows rapid recording of excitation spectra of individual molecules under ambient conditions and that is robust against blinking and bleaching. Applying the method we show that the excitation spectra of individual molecules exhibit an extreme distribution of solvatochromic shifts and distinct spectral shapes. Importantly, we demonstrate that the sensitivity and speed of the broadband technique is comparable to that of emission spectroscopy putting both techniques side-by-side in single-molecule spectroscopy. PMID:26794035

  7. Rotational Cooling of Trapped Polyatomic Molecules

    NASA Astrophysics Data System (ADS)

    Glöckner, Rosa; Prehn, Alexander; Englert, Barbara G. U.; Rempe, Gerhard; Zeppenfeld, Martin

    2015-12-01

    Controlling the internal degrees of freedom is a key challenge for applications of cold and ultracold molecules. Here, we demonstrate rotational-state cooling of trapped methyl fluoride molecules (CH3F ) by optically pumping the population of 16 M sublevels in the rotational states J =3 , 4, 5 and 6 into a single level. By combining rotational-state cooling with motional cooling, we increase the relative number of molecules in the state J =4 , K =3 , M =4 from a few percent to over 70%, thereby generating a translationally cold (≈30 mK ) and nearly pure state ensemble of about 106 molecules. Our scheme is extendable to larger sets of initial states, other final states, and a variety of molecule species, thus paving the way for internal-state control of ever-larger molecules.

  8. Aggregated Gas Molecules: Toxic to Protein?

    PubMed Central

    Zhang, Meng; Zuo, Guanghong; Chen, Jixiu; Gao, Yi; Fang, Haiping

    2013-01-01

    The biological toxicity of high levels of breathing gases has been known for centuries, but the mechanism remains elusive. Earlier work mainly focused on the influences of dispersed gas molecules dissolved in water on biomolecules. However, recent studies confirmed the existence of aggregated gas molecules at the water-solid interface. In this paper, we have investigated the binding preference of aggregated gas molecules on proteins with molecular dynamics simulations, using nitrogen (N2) gas and the Src-homology 3 (SH3) domain as the model system. Aggregated N2 molecules were strongly bound by the active sites of the SH3 domain, which could impair the activity of the protein. In contrast, dispersed N2 molecules did not specifically interact with the SH3 domain. These observations extend our understanding of the possible toxicity of aggregates of gas molecules in the function of proteins. PMID:23588597

  9. Rotational Cooling of Trapped Polyatomic Molecules.

    PubMed

    Glöckner, Rosa; Prehn, Alexander; Englert, Barbara G U; Rempe, Gerhard; Zeppenfeld, Martin

    2015-12-01

    Controlling the internal degrees of freedom is a key challenge for applications of cold and ultracold molecules. Here, we demonstrate rotational-state cooling of trapped methyl fluoride molecules (CH_{3}F) by optically pumping the population of 16 M sublevels in the rotational states J=3, 4, 5 and 6 into a single level. By combining rotational-state cooling with motional cooling, we increase the relative number of molecules in the state J=4, K=3, M=4 from a few percent to over 70%, thereby generating a translationally cold (≈30  mK) and nearly pure state ensemble of about 10^{6} molecules. Our scheme is extendable to larger sets of initial states, other final states, and a variety of molecule species, thus paving the way for internal-state control of ever-larger molecules. PMID:26684114

  10. Single molecule nanometry for biological physics

    PubMed Central

    Kim, Hajin; Ha, Taekjip

    2013-01-01

    Precision measurement is a hallmark of physics but the small length scale (~ nanometer) of elementary biological components and thermal fluctuations surrounding them challenge our ability to visualize their action. Here, we highlight the recent developments in single molecule nanometry where the position of a single fluorescent molecule can be determined with nanometer precision, reaching the limit imposed by the shot noise, and the relative motion between two molecules can be determined with ~ 0.3 nm precision at ~ 1 millisecond time resolution, and how these new tools are providing fundamental insights on how motor proteins move on cellular highways. We will also discuss how interactions between three and four fluorescent molecules can be used to measure three and six coordinates, respectively, allowing us to correlate movements of multiple components. Finally, we will discuss recent progress in combining angstrom precision optical tweezers with single molecule fluorescent detection, opening new windows for multi-dimensional single molecule nanometry for biological physics. PMID:23249673

  11. Broadband single-molecule excitation spectroscopy

    NASA Astrophysics Data System (ADS)

    Piatkowski, Lukasz; Gellings, Esther; van Hulst, Niek F.

    2016-01-01

    Over the past 25 years, single-molecule spectroscopy has developed into a widely used tool in multiple disciplines of science. The diversity of routinely recorded emission spectra does underpin the strength of the single-molecule approach in resolving the heterogeneity and dynamics, otherwise hidden in the ensemble. In early cryogenic studies single molecules were identified by their distinct excitation spectra, yet measuring excitation spectra at room temperature remains challenging. Here we present a broadband Fourier approach that allows rapid recording of excitation spectra of individual molecules under ambient conditions and that is robust against blinking and bleaching. Applying the method we show that the excitation spectra of individual molecules exhibit an extreme distribution of solvatochromic shifts and distinct spectral shapes. Importantly, we demonstrate that the sensitivity and speed of the broadband technique is comparable to that of emission spectroscopy putting both techniques side-by-side in single-molecule spectroscopy.

  12. A 3-terminal single molecule nanoscale amperometer

    NASA Astrophysics Data System (ADS)

    Hliwa, M.; Ami, S.; Joachim, C.

    2006-07-01

    A 3-terminal single molecule transducer is presented which is able to measure tunnel current intensities. The conformation of a pyrene-phenyl molecule is changed under an intramolecular inelastic current effect. This conformation change is detected by a third lateral electrode interacting also with the molecule. The full multi-channel electronic scattering matrix of the device is calculated taking into account the chemisorption of the molecule at one end and the details mechanics of the conformation change of this molecule. A semi-classical model is used to describe the intramolecular transduction effect between the electrons transferred through the molecule and its conformation change. It results a linear transduction curve between the input and the detection currents of the device for a range of tunnel current of interest for mono-molecular electronics.

  13. Open source software and web services for designing therapeutic molecules.

    PubMed

    Singla, Deepak; Dhanda, Sandeep Kumar; Chauhan, Jagat Singh; Bhardwaj, Anshu; Brahmachari, Samir K; Raghava, Gajendra P S

    2013-01-01

    Despite the tremendous progress in the field of drug designing, discovering a new drug molecule is still a challenging task. Drug discovery and development is a costly, time consuming and complex process that requires millions of dollar and 10-15 years to bring new drug molecules in the market. This huge investment and long-term process are attributed to high failure rate, complexity of the problem and strict regulatory rules, in addition to other factors. Given the availability of 'big' data with ever improving computing power, it is now possible to model systems which is expected to provide time and cost effectiveness to drug discovery process. Computer Aided Drug Designing (CADD) has emerged as a fast alternative method to bring down the cost involved in discovering a new drug. In past, numerous computer programs have been developed across the globe to assist the researchers working in the field of drug discovery. Broadly, these programs can be classified in three categories, freeware, shareware and commercial software. In this review, we have described freeware or open-source software that are commonly used for designing therapeutic molecules. Major emphasis will be on software and web services in the field of chemo- or pharmaco-informatics that includes in silico tools used for computing molecular descriptors, inhibitors designing against drug targets, building QSAR models, and ADMET properties. PMID:23647540

  14. Formation of quantum-degenerate sodium molecules.

    PubMed

    Xu, K; Mukaiyama, T; Abo-Shaeer, J R; Chin, J K; Miller, D E; Ketterle, W

    2003-11-21

    Ultracold sodium molecules were produced from an atomic Bose-Einstein condensate by ramping an applied magnetic field across a Feshbach resonance. More than 10(5) molecules were generated with a conversion efficiency of approximately 4%. Using laser light resonant with an atomic transition, the remaining atoms could be selectively removed, preventing fast collisional relaxation of the molecules. Time-of-flight analysis of the pure molecular sample yielded an instantaneous phase-space density greater than 20. PMID:14683282

  15. Circular DNA Molecules in the Genus Drosophila

    PubMed Central

    Travaglini, E. C.; Schultz, J.

    1972-01-01

    The satellite DNA's from the embryos of five species of Drosophila (D. melanogaster, D. simulans, D. nasuta, D. virilis and D. hydei) have been analyzed for the presence of closed circular duplex DNA molecules, as determined by CsCl-EBr gradients. Circular DNA molecules were found in every species but D. melanogaster. Analyses of cell fractions from adult Drosophila and organ fractions from Drosophila larvae show that fractions containing mitochondria are highly enriched in these molecules. PMID:4643820

  16. A new interstellar molecule - Tricarbon monoxide

    NASA Technical Reports Server (NTRS)

    Matthews, H. E.; Irvine, W. M.; Friberg, P.; Brown, R. D.; Godfrey, P. D.

    1984-01-01

    The C3O molecule, whose pure rotational spectrum has only recently been studied in the laboratory, has been detected in the cold, dark interstellar Taurus Molecular Cloud 1. Since C3O is the first interstelar carbon chain molecule to contain oxygen, its existence places an important new constraint on chemical schemes for cold interstellar clouds. The abundance of C3O can be understood in terms of purely gas-phase ion-molecule chemistry.

  17. Production and Trapping of Ultracold Polar Molecules

    SciTech Connect

    David, DeMille

    2015-04-21

    We report a set of experiments aimed at the production and trapping of ultracold polar molecules. We begin with samples of laser-cooled and trapped Rb and Cs atoms, and bind them together to form polar RbCs molecules. The binding is accomplished via photoassociation, which uses a laser to catalyze the sticking process. We report results from investigation of a new pathway for photoassociation that can produce molecules in their absolute ground state of vibrational and rotational motion. We also report preliminary observations of collisions between these ground-state molecules and co-trapped atoms.

  18. Small Molecule based Musculoskeletal Regenerative Engineering

    PubMed Central

    Lo, Kevin W.-H.; Jiang, Tao; Gagnon, Keith A.; Nelson, Clarke; Laurencin, Cato T.

    2014-01-01

    Clinicians and scientists working in the field of regenerative engineering are actively investigating a wide range of methods to promote musculoskeletal tissue regeneration. Small molecule-mediated tissue regeneration is emerging as a promising strategy for regenerating various musculoskeletal tissues and a large number of small molecule compounds have been recently discovered as potential bioactive molecules for musculoskeletal tissue repair and regeneration. In this review, we summarize the recent literature encompassing the past four years in the area of small bioactive molecule for promoting repair and regeneration of various musculoskeletal tissues including bone, muscle, cartilage, tendon, and nerve. PMID:24405851

  19. Circularly Polarized Luminescence from Simple Organic Molecules.

    PubMed

    Sánchez-Carnerero, Esther M; Agarrabeitia, Antonia R; Moreno, Florencio; Maroto, Beatriz L; Muller, Gilles; Ortiz, María J; de la Moya, Santiago

    2015-09-21

    This article aims to show the identity of "circularly polarized luminescent active simple organic molecules" as a new concept in organic chemistry due to the potential interest of these molecules, as availed by the exponentially growing number of research articles related to them. In particular, it describes and highlights the interest and difficulty in developing chiral simple (small and non-aggregated) organic molecules able to emit left- or right-circularly polarized light efficiently, the efforts realized up to now to reach this challenging objective, and the most significant milestones achieved to date. General guidelines for the preparation of these interesting molecules are also presented. PMID:26136234

  20. Electron microscopy of low iodinated thyroglobulin molecules.

    PubMed

    Berg, G; Ekholm, R

    1975-04-29

    Thyroglobulin molecules were studied in the electron microscope with negative staining technique. In a first series of experiments samples of thyroglobulin varying in iodine content from 0.5 to 0.03% were prepared from the thyroids of mice and rats kept on iodine-poor diets. All samples contained thyroglobulin molecules of the normal ovoid shape, not deviating in size or shape from molecules obtained from normal thyroids. However, in addition, another type of molecule having a cylindrical shape was observed in all samples. The proportion of these cylindrical molecules increased from a few per cent in the moderately iodine-poor thyroglobulin samples to more than 80% in the highly iodine-deficient thyroglobulin (0.03%). In a second series of experiments extremely iodine-poor thyroglobulin (smaller than 0.005%) was obtained from propylthiouracil-treated rats. In these preparations practically all molecules had a cylindrical shape. These samples also contained smaller particles interpreted to be dissociation products. The cylindrical molecules were of two types, one appearing compact and measuring 250 times 135 A (length times diameter) and the other appearing porous and having a length of 145 and a diameter of 205 A. It is concluded that the cylindrical molecules represent non- or low-iodinated thyroglobulin and it is suggested that the porous cylindrical molecule is an unfolded form of the compact cylinder. PMID:1138879

  1. Design of water molecule and its surrounding

    NASA Astrophysics Data System (ADS)

    Danylo, R. I.; Okhrimenko, B. A.; Yablochkova, K. S.

    2015-02-01

    Hydrogen bonds and their fluctuations are one of the factors that determine the unique properties of water [1]. Building models of formation and rupture of hydrogen bonds due to non-eigen vibrations of a molecule of water is to a large extent determined by the availability of accurate information on the geometric structure of the water molecule. Geometric parameters of the water molecule have been well studied for the gaseous state. This was aided by the possibility of an experimental study of the regularities in the rotational spectra of molecules. However, some questions about the geometry of the water molecule in the liquid state remain unanswered. For example, many sources state that the valence angle of the water molecule decreases during the transition into the liquid state [2]. Based on the experimental data of molecular vibration spectra in D2O and H2O molecules [3], the authors have estimated valence angle of water in the liquid state. Consequently, the value of the valence angle of water in liquid state was determined to be (89 +/-2)°. A question of determination of libration vibrations of water molecule, as well as the analysis of its consequent inversion doubling, based on the new information on the equilibrium angle of the water molecules in the liquid state, constitutes an interest and is discussed in the present paper.

  2. Halogen bonds in biological molecules

    PubMed Central

    Auffinger, Pascal; Hays, Franklin A.; Westhof, Eric; Ho, P. Shing

    2004-01-01

    Short oxygen–halogen interactions have been known in organic chemistry since the 1950s and recently have been exploited in the design of supramolecular assemblies. The present survey of protein and nucleic acid structures reveals similar halogen bonds as potentially stabilizing inter- and intramolecular interactions that can affect ligand binding and molecular folding. A halogen bond in biomolecules can be defined as a short CX···OY interaction (CX is a carbon-bonded chlorine, bromine, or iodine, and OY is a carbonyl, hydroxyl, charged carboxylate, or phosphate group), where the X···O distance is less than or equal to the sums of the respective van der Waals radii (3.27 Å for Cl···O, 3.37Å for Br···O, and 3.50 Å for I···O) and can conform to the geometry seen in small molecules, with the CX···O angle ≈165° (consistent with a strong directional polarization of the halogen) and the X···OY angle ≈120°. Alternative geometries can be imposed by the more complex environment found in biomolecules, depending on which of the two types of donor systems are involved in the interaction: (i) the lone pair electrons of oxygen (and, to a lesser extent, nitrogen and sulfur) atoms or (ii) the delocalized π -electrons of peptide bonds or carboxylate or amide groups. Thus, the specific geometry and diversity of the interacting partners of halogen bonds offer new and versatile tools for the design of ligands as drugs and materials in nanotechnology. PMID:15557000

  3. Halogen bonds in biological molecules.

    PubMed

    Auffinger, Pascal; Hays, Franklin A; Westhof, Eric; Ho, P Shing

    2004-11-30

    Short oxygen-halogen interactions have been known in organic chemistry since the 1950s and recently have been exploited in the design of supramolecular assemblies. The present survey of protein and nucleic acid structures reveals similar halogen bonds as potentially stabilizing inter- and intramolecular interactions that can affect ligand binding and molecular folding. A halogen bond in biomolecules can be defined as a short C-X...O-Y interaction (C-X is a carbon-bonded chlorine, bromine, or iodine, and O-Y is a carbonyl, hydroxyl, charged carboxylate, or phosphate group), where the X...O distance is less than or equal to the sums of the respective van der Waals radii (3.27 A for Cl...O, 3.37 A for Br...O, and 3.50 A for I...O) and can conform to the geometry seen in small molecules, with the C-X...O angle approximately 165 degrees (consistent with a strong directional polarization of the halogen) and the X...O-Y angle approximately 120 degrees . Alternative geometries can be imposed by the more complex environment found in biomolecules, depending on which of the two types of donor systems are involved in the interaction: (i) the lone pair electrons of oxygen (and, to a lesser extent, nitrogen and sulfur) atoms or (ii) the delocalized pi -electrons of peptide bonds or carboxylate or amide groups. Thus, the specific geometry and diversity of the interacting partners of halogen bonds offer new and versatile tools for the design of ligands as drugs and materials in nanotechnology. PMID:15557000

  4. Submillimeter Spectroscopy of Hydride Molecules

    NASA Astrophysics Data System (ADS)

    Phillips, T. G.

    1998-05-01

    Simple hydride molecules are of great importance in astrophysics and astrochemistry. Physically they dominate the cooling of dense, warm phases of the ISM, such as the cores and disks of YSOs. Chemically they are often stable end points of chemical reactions, or may represent important intermediate stages of the reaction chains, which can be used to test the validity of the process. Through the efforts of astronomers, physicists, chemists, and laboratory spectroscopists we have an approximate knowledge of the abundance of some of the important species, but a great deal of new effort will be required to achieve the comprehensive and accurate data set needed to determine the energy balance and firmly establish the chemical pathways. Due to the low moment of inertia, the hydrides rotate rapidly and so have their fundamental spectral lines in the submillimeter. Depending on the cloud geometry and temperature profile they may be observed in emission or absorption. Species such as HCl, HF, OH, CH, CH(+) , NH_2, NH_3, H_2O, H_2S, H_3O(+) and even H_3(+) have been detected, but this is just a fraction of the available set. Also, most deduced abundances are not nearly sufficiently well known to draw definitive conclusions about the chemical processes. For example, the most important coolant for many regions, H_2O, has a possible range of deduced abundance of a factor of 1000. The very low submillimeter opacity at the South Pole site will be a significant factor in providing a new capabilty for interstellar hydride spectroscopy. The new species and lines made available in this way will be discussed.

  5. Completed Optimised Structure of Threonine Molecule by Fuzzy Logic Modelling

    NASA Astrophysics Data System (ADS)

    Sahiner, Ahmet; Ucun, Fatih; Kapusuz, Gulden; Yilmaz, Nurullah

    2016-04-01

    In this study we applied the fuzzy logic approach in order to model the energy depending on the two torsion angles for the threonine (C4H9NO3) molecule. The model is set up according to theoretical results obtained by the density functional theory (B3LYP) with a 6-31 G(d) basic set on a Gausian program. We aimed to determine the best torsion angle values providing the energy of the molecule minimum by a fuzzy logic approach and to compare them with the density functional theory results. It was concluded that the fuzzy logic approach gives information about the untested data and its best value which are expensive and time-consuming to obtain by other methods and experimentation.

  6. Computational analysis of the reactive properties of some nitrosoaromatic molecules

    SciTech Connect

    Politzer, P.; Bar-Adon, R.

    1987-04-09

    The interactions of a nitroso (NO) substituent with an aromatic ring and with an amino group on that ring, and the manner in which these affect the overall molecular reactivity, have been studied by ab initio SCF molecular orbital calculations. The Gaussian 82 program was used to first optimize the structures of nitrosobenzene and the three isomeric nitrosoanilines, at the 3-21G level, and then to compute the STO-5G molecular electrostatic potentials. The NO was found to deactivate the ring toward electrophilic attack, even in the presence of NH/sub 2/, although the directing properties of the latter are evident. For each molecule, the strongest negative potential is associated with the lone pair of the nitroso nitrogen. All the molecules show buildups of positive potential above the C-NO portions, within the C-N-O angles; these are interpreted as possible routes for nucleophilic attack.

  7. Carbon Nanotube Biosensors for Space Molecule Detection and Clinical Molecular Diagnostics

    NASA Technical Reports Server (NTRS)

    Han, Jie

    2001-01-01

    Both space molecule detection and clinical molecule diagnostics need to develop ultra sensitive biosensors for detection of less than attomole molecules such as amino acids for DNA. However all the electrode sensor systems including those fabricated from the existing carbon nanotubes, have a background level of nA (nanoAmp). This has limited DNA or other molecule detection to nA level or molecules whose concentration is, much higher than attomole level. A program has been created by NASA and NCI (National Cancer Institute) to exploit the possibility of carbon nanotube based biosensors to solve this problem for both's interest. In this talk, I will present our effort on the evaluation and novel design of carbon nanotubes as electrode biosensors with strategies to minimize background currents while maximizing signal intensity.The fabrication of nanotube electrode arrays, immobilization of molecular probes on nanotube electrodes and in vitro biosensor testing will also be discussed.

  8. Spin polarization effect for Fe2 molecule

    NASA Astrophysics Data System (ADS)

    Yan, Shi-Ying; Zhu, Zheng-He

    2006-07-01

    This paper uses the density functional theory (DFT)(B3p86) of Gaussian03 to optimize the structure of Fe2 molecule. The result shows that the ground state for Fe2 molecule is a 9-multiple state, which shows spin polarization effect of Fe2 molecule of transition metal elements for the first time. Meanwhile, we have not found any spin pollution because the wavefunction of the ground state does not mingle with wavefunctions with higher energy states. So, that the ground state for Fe2 molecule is a 9-multiple state is indicative of the spin polarization effect of Fe2 molecule of transition metal elements. That is, there exist 8 parallel spin electrons. The non-conjugated electron is greatest in number. These electrons occupy different spacious tracks, so that the energy of the Fe2 molecule is minimized. It can be concluded that the effect of parallel spin of the Fe2 molecule is larger than the effect of the conjugated molecule, which is obviously related to the effect of electron d delocalization. In addition, the Murrell-Sorbie potential functions with the parameters for the ground state and other states of Fe2 molecule are derived. Dissociation energy De for the ground state of Fe2 molecule is 2.8586ev, equilibrium bond length Re is 0.2124nm, vibration frequency ωe is 336.38 cm-1. Its force constants f2, f3, and f4 are 1.8615aJ.nm-2, -8.6704aJ.nm-3, 29.1676aJ.nm-4 respectively. The other spectroscopic data for the ground state of Fe2 molecule ωeχe,Be, αe are 1.5461 cm-1, 0.1339 cm-1, 7.3428×10-4 cm-1 respectively.

  9. The Distribution of Solubilized Molecules among Micelles.

    ERIC Educational Resources Information Center

    Miller, Dennis J.

    1978-01-01

    Conflicting views have been put forward on the derivation of the distribution of solubilized molecules among micelles. This stems from failure to consider the arrangement of the solubilized molecules in the micelles. In the treatment presented enthalpy effects are ignored as they are not amenable to a simple general theory. (Author/BB)

  10. Small Molecules in the Cone Snail Arsenal.

    PubMed

    Neves, Jorge L B; Lin, Zhenjian; Imperial, Julita S; Antunes, Agostinho; Vasconcelos, Vitor; Olivera, Baldomero M; Schmidt, Eric W

    2015-10-16

    Cone snails are renowned for producing peptide-based venom, containing conopeptides and conotoxins, to capture their prey. A novel small-molecule guanine derivative with unprecedented features, genuanine, was isolated from the venom of two cone snail species. Genuanine causes paralysis in mice, indicating that small molecules and not just polypeptides may contribute to the activity of cone snail venom. PMID:26421741

  11. Tumor suppressor molecules and methods of use

    DOEpatents

    Welch, Peter J.; Barber, Jack R.

    2004-09-07

    The invention provides substantially pure tumor suppressor nucleic acid molecules and tumor suppressor polypeptides. The invention also provides hairpin ribozymes and antibodies selective for these tumor suppressor molecules. Also provided are methods of detecting a neoplastic cell in a sample using detectable agents specific for the tumor suppressor nucleic acids and polypeptides.

  12. Energy Transfer Involving Diatomic Molecules.

    NASA Astrophysics Data System (ADS)

    Gibbons, John Paul

    three colliding pairs, the experimental results lie between the results calculated for the same two sets of potential parameters. These parameters were those calculated to match the short range Lennard-Jones potential and a set obtained by a theoretical Thomas-Fermi treatment of the molecules.

  13. Chemical principles of single-molecule electronics

    NASA Astrophysics Data System (ADS)

    Su, Timothy A.; Neupane, Madhav; Steigerwald, Michael L.; Venkataraman, Latha; Nuckolls, Colin

    2016-03-01

    The field of single-molecule electronics harnesses expertise from engineering, physics and chemistry to realize circuit elements at the limit of miniaturization; it is a subfield of nanoelectronics in which the electronic components are single molecules. In this Review, we survey the field from a chemical perspective and discuss the structure-property relationships of the three components that form a single-molecule junction: the anchor, the electrode and the molecular bridge. The spatial orientation and electronic coupling between each component profoundly affect the conductance properties and functions of the single-molecule device. We describe the design principles of the anchor group, the influence of the electronic configuration of the electrode and the effect of manipulating the structure of the molecular backbone and of its substituent groups. We discuss single-molecule conductance switches as well as the phenomenon of quantum interference and then trace their fundamental roots back to chemical principles.

  14. Relationships between dipole moments of diatomic molecules.

    PubMed

    Hou, Shilin; Bernath, Peter F

    2015-02-14

    The dipole moment is one of the most important physical properties of a molecule. We present a combination rule for the dipole moments of related diatomic molecules. For molecules AB, AX, BY, and XY from two different element groups in the periodic table, if their elements make a small parallelogram, reliable predictions can be obtained. Our approach is particularly useful for systems with heavy atoms. For a large set of molecules tested, the average difference of the prediction from experimental data is less than 0.2 debye (D). The dipole moments for heavy molecules such as GaCl, InBr, SrCl, and SrS, for which no experimental data are available at present, are predicted to be 3.17, 3.76, 3.85 and 11.54 D, respectively. PMID:25588998

  15. Extracting Models in Single Molecule Experiments

    NASA Astrophysics Data System (ADS)

    Presse, Steve

    2013-03-01

    Single molecule experiments can now monitor the journey of a protein from its assembly near a ribosome to its proteolytic demise. Ideally all single molecule data should be self-explanatory. However data originating from single molecule experiments is particularly challenging to interpret on account of fluctuations and noise at such small scales. Realistically, basic understanding comes from models carefully extracted from the noisy data. Statistical mechanics, and maximum entropy in particular, provide a powerful framework for accomplishing this task in a principled fashion. Here I will discuss our work in extracting conformational memory from single molecule force spectroscopy experiments on large biomolecules. One clear advantage of this method is that we let the data tend towards the correct model, we do not fit the data. I will show that the dynamical model of the single molecule dynamics which emerges from this analysis is often more textured and complex than could otherwise come from fitting the data to a pre-conceived model.

  16. Small-molecule-dependent split aptamer ligation.

    PubMed

    Sharma, Ashwani K; Heemstra, Jennifer M

    2011-08-17

    Here we describe the first use of small-molecule binding to direct a chemical reaction between two nucleic acid strands. The reported reaction is a ligation between two fragments of a DNA split aptamer using strain-promoted azide-alkyne cycloaddition. Utilizing the split aptamer for cocaine, we demonstrate small-molecule-dependent ligation that is dose-dependent over a wide range of cocaine concentrations and is compatible with complex biological fluids such as human blood serum. Moreover, studies of split aptamer ligation at varying salt concentrations and using structurally similar analogues of cocaine have revealed new insight into the assembly and small-molecule binding properties of the cocaine split aptamer. The ability to translate the presence of a small-molecule target into the output of DNA ligation is anticipated to enable the development of new, broadly applicable small-molecule detection assays. PMID:21761903

  17. Single-Molecule Solvation-Shell Sensing

    NASA Astrophysics Data System (ADS)

    Leary, E.; Höbenreich, H.; Higgins, S. J.; van Zalinge, H.; Haiss, W.; Nichols, R. J.; Finch, C. M.; Grace, I.; Lambert, C. J.; McGrath, R.; Smerdon, J.

    2009-02-01

    We present a new route to single-molecule sensing via solvation shells surrounding a current-carrying backbone molecule. As an example, we show that the presence of a water solvation shell “gates” the conductance of a family of oligothiophene-containing molecular wires, and that the longer the oligothiophene, the larger is the effect. For the longest example studied, the molecular conductance is over 2 orders of magnitude larger in the presence of a shell comprising just 10 water molecules. A first principles theoretical investigation of electron transport through the molecules, using the nonequilibrium Green’s function method, shows that water molecules interact directly with the thiophene rings, significantly shifting transport resonances and greatly increasing the conductance. This reversible effect is confirmed experimentally through conductance measurements performed in the presence of moist air and dry argon.

  18. The symmetry of single-molecule conduction.

    PubMed

    Solomon, Gemma C; Gagliardi, Alessio; Pecchia, Alessandro; Frauenheim, Thomas; Di Carlo, Aldo; Reimers, Jeffrey R; Hush, Noel S

    2006-11-14

    We introduce the conductance point group which defines the symmetry of single-molecule conduction within the nonequilibrium Green's function formalism. It is shown, either rigorously or to within a very good approximation, to correspond to a molecular-conductance point group defined purely in terms of the properties of the conducting molecule. This enables single-molecule conductivity to be described in terms of key qualitative chemical descriptors that are independent of the nature of the molecule-conductor interfaces. We apply this to demonstrate how symmetry controls the conduction through 1,4-benzenedithiol chemisorbed to gold electrodes as an example system, listing also the molecular-conductance point groups for a range of molecules commonly used in molecular electronics research. PMID:17115774

  19. Electronic and thermal properties of Biphenyl molecules

    NASA Astrophysics Data System (ADS)

    Medina, F. G.; Ojeda, J. H.; Duque, C. A.; Laroze, D.

    2015-11-01

    Transport properties of a single Biphenyl molecule coupled to two contacts are studied. We characterise this system by a tight-binding Hamiltonian. Based on the non-equilibrium Green's functions technique with a Landauer-Büttiker formalism the transmission probability, current and thermoelectrical power are obtained. We show that the Biphenyl molecule may have semiconductor behavior for certain values of the electrode-molecule-electrode junctions and different values of the angle between the two rings of the molecule. In addition, the density of states (DOS) is calculated to compare the bandwidths with the profile of the transmission probability. DOS allows us to explain the asymmetric shape with respect to the molecule's Fermi energy.

  20. Superresolution Imaging using Single-Molecule Localization

    PubMed Central

    Patterson, George; Davidson, Michael; Manley, Suliana; Lippincott-Schwartz, Jennifer

    2013-01-01

    Superresolution imaging is a rapidly emerging new field of microscopy that dramatically improves the spatial resolution of light microscopy by over an order of magnitude (∼10–20-nm resolution), allowing biological processes to be described at the molecular scale. Here, we discuss a form of superresolution microscopy based on the controlled activation and sampling of sparse subsets of photoconvertible fluorescent molecules. In this single-molecule based imaging approach, a wide variety of probes have proved valuable, ranging from genetically encodable photoactivatable fluorescent proteins to photoswitchable cyanine dyes. These have been used in diverse applications of superresolution imaging: from three-dimensional, multicolor molecule localization to tracking of nanometric structures and molecules in living cells. Single-molecule-based superresolution imaging thus offers exciting possibilities for obtaining molecular-scale information on biological events occurring at variable timescales. PMID:20055680

  1. Attachment of second harmonic-active moiety to molecules for detection of molecules at interfaces

    DOEpatents

    Salafsky, Joshua S.; Eisenthal, Kenneth B.

    2005-10-11

    This invention provides methods of detecting molecules at an interface, which comprise labeling the molecules with a second harmonic-active moiety and detecting the labeled molecules at the interface using a surface selective technique. The invention also provides methods for detecting a molecule in a medium and for determining the orientation of a molecular species within a planar surface using a second harmonic-active moiety and a surface selective technique.

  2. Enrichment of Inflammatory IL-17 and TNF-α Secreting CD4+ T Cells within Colorectal Tumors despite the Presence of Elevated CD39+ T Regulatory Cells and Increased Expression of the Immune Checkpoint Molecule, PD-1

    PubMed Central

    Dunne, Margaret R.; Ryan, Ciara; Nolan, Bláthnaid; Tosetto, Miriam; Geraghty, Robert; Winter, Des C.; O’Connell, P. Ronan; Hyland, John M.; Doherty, Glen A.; Sheahan, Kieran; Ryan, Elizabeth J.; Fletcher, Jean M.

    2016-01-01

    T cell infiltration into colorectal tumors has been shown to correlate with improved patient outcomes. However, more detailed information on the makeup and relationships between the infiltrating T cell subsets is lacking. We therefore correlated the extent of immune infiltration into colorectal tumors with the frequencies of various T cell subsets. We prospectively recruited 22 patients at the time of surgical resection for colorectal cancer. The Klintrup–Mäkinen (KM) score was used to estimate the extent of immune infiltration into colorectal tumors. The frequencies of CD4 and CD8 T cells that produced cytokines or expressed the inhibitory molecule programed cell death 1 (PD-1) were determined by flow cytometry in colorectal tumor and matched uninvolved colonic tissue. In addition, the frequency of CD4 regulatory T cell (Treg) subsets was determined. An increased frequency of CD4 T cells producing IL-17 (Th17 cells) was observed in colorectal tumor tissue compared with adjacent uninvolved tissue. These Th17 cells mostly coproduced TNF-α, but not IFN-γ. IL-17 expression correlated positively with TNF-α and IL-10. Increased expression of the immune checkpoint molecule PD-1 was found in colorectal tumors compared with adjacent uninvolved tissue. There was a negative correlation between expression of PD-1 and IFN-γ, but not IL-17, for both CD4+ and CD8+ T cells. CD4+CD25+CD127lo and CD4+CD25+CD127loFoxP3+CD39+ Treg cells were enriched in colorectal tumors. A positive correlation between KM score and percentage CD4+CD25+CD127lo Treg cells was observed in tumors, suggesting that increased immune infiltration is associated with an increased proportion of Treg cells. In addition, there was a negative correlation between the frequency of CD4+CD25+CD127lo Treg cells and the expression of IFN-γ and IL-2, but not IL-17, in tumors. Taken together, these data suggest that both PD-1 expressing T cells and Treg cells within the tumor may have a suppressive effect on T

  3. High Harmonic Generation from Rotationally Excited Molecules

    NASA Astrophysics Data System (ADS)

    Lock, Robynne M.

    2011-12-01

    High harmonic generation (HHG) is understood through a three-step model. A strong laser field ionizes an atom or molecule. The free electron propagates in the laser field and may recombine with the atom or molecule leading to the generation of extreme ultraviolet or soft x-ray light at odd harmonics of the fundamental. Since the wavelength of the recombining electron is on the order of internuclear distances in molecules, HHG acts as a probe of molecular structure and dynamics. Conversely, control of the molecules leads to control of the properties (intensity, phase, and polarization) of the harmonic emission. Rotationally exciting molecules provides field-free molecular alignment at time intervals corresponding to fractions of the rotational period of the molecule. Alignment is necessary for understanding how the harmonic emission depends on molecular structure and alignment. Additionally, HHG acts as a probe of the rotational wavepackets. This thesis reports three experiments on HHG from rotationally excited molecules. Before we can use HHG as a probe of complex molecular dynamics or control harmonic properties through molecules, the harmonic emission from aligned, linear molecules must first be understood. To that end, the first experiment measures the intensity and phase of harmonics generated from N 2O and N2 near times of strong alignment revealing interferences during recombination. The second experiment demonstrates HHG as a sensitive probe of rotational wavepacket dynamics in CO2 and N2O, revealing new revival features not detected by any other probe. The final experiment focuses on understanding and controlling the polarization state of the harmonic emission. Generating elliptically polarized harmonics would be very useful for probing molecular and materials systems. We observe an elliptical dichroism in polarization-resolved measurements of the harmonic emission from aligned N2 and CO2 molecules, revealing evidence for electron-hole dynamics between the

  4. Search for complex organic molecules in space

    NASA Astrophysics Data System (ADS)

    Ohishi, Masatoshi

    2016-07-01

    It was 1969 when the first organic molecule in space, H2CO, was discovered. Since then many organic molecules were discovered by using the NRAO 11 m (upgraded later to 12 m), Nobeyama 45 m, IRAM 30 m, and other highly sensitive radio telescopes as a result of close collaboration between radio astronomers and microwave spectroscopists. It is noteworthy that many famous organic molecules such as CH3OH, C2H5OH, (CH3)2O and CH3NH2 were detected by 1975. Organic molecules were found in so-called hot cores where molecules were thought to form on cold dust surfaces and then to evaporate by the UV photons emitted from the central star. These days organic molecules are known to exist not only in hot cores but in hot corinos (a warm, compact molecular clump found in the inner envelope of a class 0 protostar) and even protoplanetary disks. As was described above, major organic molecules were known since 1970s. It was very natural that astronomers considered a relationship between organic molecules in space and the origin of life. Several astronomers challenged to detect glycine and other prebiotic molecules without success. ALMA is expected to detect such important materials to further consider the gexogenous deliveryh hypothesis. In this paper I summarize the history in searching for complex organic molecules together with difficulties in observing very weak signals from larger species. The awfully long list of references at the end of this article may be the most useful part for readers who want to feel the exciting discovery stories.

  5. Low energy positron interactions with biological molecules

    NASA Astrophysics Data System (ADS)

    Wanniarachchi, Indika L.

    Calculations of the positron density distribution which can be used for positrons bound to midsize and larger molecules have been tested for smaller molecules and subsequently applied to investigate the most likely e +e-- annihilation sites for positrons interacting with biological molecules containing C, H, O, and N. In order to allow consideration of positrons bound to extended molecules with regions of different character and no particular symmetry, atom-centered positron basis sets of Gaussian-type functions were developed for positrons bound to molecules containing O, N, C, H, Li, Na, and Be. Testing shows that there is no need to scale the positron basis functions to take into account different effective charges on the atoms in different molecules. Even at the HF level of theory the calculated positron and the contact density of e+LiH system is in qualitative agreement with the most accurate calculation was done in ECG method. Also it has been found that for larger biological molecules such as derivation of formaldehyde can leave out positron basis sets centered on H atoms and still get qualitatively acceptable contact density distribution. According to our results, the electronic and positronic wavefunctions have the most overlap in the regions of most negative electrostatic potential in the parent molecule, and we can expect that a positron bound to the molecule will be more likely to annihilate with one of the electrons in these regions. Also we find that the highest energy occupied electronic orbital often does not make the largest contribution to e+e -- annihilation, and that the energy liberated by subsequent electronic relaxation is sufficient to break the backbone in several places in di-peptides and other organic molecules.

  6. Cytochrome c Is Released in a Reactive Oxygen Species-Dependent Manner and Is Degraded via Caspase-Like Proteases in Tobacco Bright-Yellow 2 Cells en Route to Heat Shock-Induced Cell Death1

    PubMed Central

    Vacca, Rosa Anna; Valenti, Daniela; Bobba, Antonella; Merafina, Riccardo Sandro; Passarella, Salvatore; Marra, Ersilia

    2006-01-01

    To gain some insight into the mechanism of plant programmed cell death, certain features of cytochrome c (cyt c) release were investigated in heat-shocked tobacco (Nicotiana tabacum) Bright-Yellow 2 cells in the 2- to 6-h time range. We found that 2 h after heat shock, cyt c is released from intact mitochondria into the cytoplasm as a functionally active protein. Such a release did not occur in the presence of superoxide anion dismutase and catalase, thus showing that it depends on reactive oxygen species (ROS). Interestingly, ROS production due to xanthine plus xanthine oxidase results in cyt c release in sister control cultures. Maximal cyt c release was found 2 h after heat shock; later, activation of caspase-3-like protease was found to increase with time. Activation of this protease did not occur in the presence of ROS scavenger enzymes. The released cyt c was found to be progressively degraded in a manner prevented by either the broad-range caspase inhibitor (zVAD-fmk) or the specific inhibitor of caspase-3 (AC-DEVD-CHO), which have no effect on cyt c release. In the presence of these inhibitors, a significant increase in survival of the cells undergoing programmed cell death was found. We conclude that ROS can trigger release of cyt c, but do not cause cell death, which requires caspase-like activation. PMID:16531480

  7. Spectroscopic and dynamical studies of highly energized small polyatomic molecules

    SciTech Connect

    Field, R.W.; Silbey, R.J.

    1993-12-01

    The authors have initiated a program to perform spectroscopic and dynamic studies of small molecules. Large amplitude motions in excited acetylene were discussed along with plans to record the dispersed fluorescence (DF) and the stimulated emission pumping (SEP) spectra. SEP spectra were reported for the formyl radical. A Fourier transform spectrometer was discussed with respect to its ability to probe the structure of radicals. This instrument is capable of performing studies using various techniques such as magnetic rotation spectroscopy and sub-Doppler sideband-OODR Zeman (SOODRZ) spectroscopy.

  8. Electron-driven excitations and dissociation of molecules

    SciTech Connect

    Miller, Greg; Orel, Ann E.

    2015-02-13

    This program studied how energy is interchanged in electron and photon collisions with molecules leading to ex-citation and dissociation. Modern ab initio techniques, both for the photoionization and electron scattering, and the subsequent nuclear dynamics studies, are used to accurately treat these problems. This work addresses vibrational ex-citation and dissociative attachment following electron impact, and the dynamics following inner shell photoionzation. These problems are ones for which a full multi-dimensional treatment of the nuclear dynamics is essential and where non-adiabatic effects are expected to be important.

  9. CHEMICAL ACTIVATION OF MOLECULES BY METALS: EXPERIMENTAL STUDIES OF ELECTRON DISTRIBUTIONS AND BONDING

    SciTech Connect

    LICHTENBERGER, DENNIS L.

    2002-03-26

    This research program is directed at obtaining detailed experimental information on the electronic interactions between metals and organic molecules. These interactions provide low energy pathways for many important chemical and catalytic processes. A major feature of the program is the continued development and application of our special high-resolution valence photoelectron spectroscopy (UPS), and high-precision X-ray core photoelectron spectroscopy (XPS) instrumentation for study of organometallic molecules in the gas phase. The study involves a systematic approach towards understanding the interactions and activation of bound carbonyls, C-H bonds, methylenes, vinylidenes, acetylides, alkenes, alkynes, carbenes, carbynes, alkylidenes, alkylidynes, and others with various monometal, dimetal, and cluster metal species. Supporting ligands include -aryls, alkoxides, oxides, and phosphines. We are expanding our studies of both early and late transition metal species and electron-rich and electron-poor environments in order to more completely understand the electronic factors that serve to stabilize particular organic fragments and intermediates on metals. Additional new directions for this program are being taken in ultra-high vacuum surface UPS, XPS, scanning tunneling microscopy (STM) and atomic force microscopy (AFM) experiments on both physisorbed and chemisorbed organometallic thin films. The combination of these methods provides additional electronic structure information on surface-molecule and molecule-molecule interactions. A very important general result emerging from this program is the identification of a close relationship between the ionization energies of the species and the thermodynamics of the chemical and catalytic reactions of these systems.

  10. Single Molecule Spectroscopy of Electron Transfer

    SciTech Connect

    Michael Holman; Ling Zang; Ruchuan Liu; David M. Adams

    2009-10-20

    The objectives of this research are threefold: (1) to develop methods for the study electron transfer processes at the single molecule level, (2) to develop a series of modifiable and structurally well defined molecular and nanoparticle systems suitable for detailed single molecule/particle and bulk spectroscopic investigation, (3) to relate experiment to theory in order to elucidate the dependence of electron transfer processes on molecular and electronic structure, coupling and reorganization energies. We have begun the systematic development of single molecule spectroscopy (SMS) of electron transfer and summaries of recent studies are shown. There is a tremendous need for experiments designed to probe the discrete electronic and molecular dynamic fluctuations of single molecules near electrodes and at nanoparticle surfaces. Single molecule spectroscopy (SMS) has emerged as a powerful method to measure properties of individual molecules which would normally be obscured in ensemble-averaged measurement. Fluctuations in the fluorescence time trajectories contain detailed molecular level statistical and dynamical information of the system. The full distribution of a molecular property is revealed in the stochastic fluctuations, giving information about the range of possible behaviors that lead to the ensemble average. In the case of electron transfer, this level of understanding is particularly important to the field of molecular and nanoscale electronics: from a device-design standpoint, understanding and controlling this picture of the overall range of possible behaviors will likely prove to be as important as designing ia the ideal behavior of any given molecule.

  11. Single-molecule junctions beyond electronic transport

    NASA Astrophysics Data System (ADS)

    Aradhya, Sriharsha V.; Venkataraman, Latha

    2013-06-01

    The idea of using individual molecules as active electronic components provided the impetus to develop a variety of experimental platforms to probe their electronic transport properties. Among these, single-molecule junctions in a metal-molecule-metal motif have contributed significantly to our fundamental understanding of the principles required to realize molecular-scale electronic components from resistive wires to reversible switches. The success of these techniques and the growing interest of other disciplines in single-molecule-level characterization are prompting new approaches to investigate metal-molecule-metal junctions with multiple probes. Going beyond electronic transport characterization, these new studies are highlighting both the fundamental and applied aspects of mechanical, optical and thermoelectric properties at the atomic and molecular scales. Furthermore, experimental demonstrations of quantum interference and manipulation of electronic and nuclear spins in single-molecule circuits are heralding new device concepts with no classical analogues. In this Review, we present the emerging methods being used to interrogate multiple properties in single molecule-based devices, detail how these measurements have advanced our understanding of the structure-function relationships in molecular junctions, and discuss the potential for future research and applications.

  12. Tuning the Magnetic Anisotropy of Single Molecules.

    PubMed

    Heinrich, Benjamin W; Braun, Lukas; Pascual, Jose I; Franke, Katharina J

    2015-06-10

    The magnetism of single atoms and molecules is governed by the atomic scale environment. In general, the reduced symmetry of the surrounding splits the d states and aligns the magnetic moment along certain favorable directions. Here, we show that we can reversibly modify the magnetocrystalline anisotropy by manipulating the environment of single iron(II) porphyrin molecules adsorbed on Pb(111) with the tip of a scanning tunneling microscope. When we decrease the tip-molecule distance, we first observe a small increase followed by an exponential decrease of the axial anisotropy on the molecules. This is in contrast to the monotonous increase observed earlier for the same molecule with an additional axial Cl ligand ( Nat. Phys. 2013 , 9 , 765 ). We ascribe the changes in the anisotropy of both species to a deformation of the molecules in the presence of the attractive force of the tip, which leads to a change in the d level alignment. These experiments demonstrate the feasibility of a precise tuning of the magnetic anisotropy of an individual molecule by mechanical control. PMID:25942560

  13. Trapping and manipulating single molecules of DNA

    NASA Astrophysics Data System (ADS)

    Shon, Min Ju

    This thesis presents the development and application of nanoscale techniques to trap and manipulate biomolecules, with a focus on DNA. These methods combine single-molecule microscopy and nano- and micro-fabrication to study biophysical properties of DNA and proteins. The Dimple Machine is a lab-on-a-chip device that can isolate and confine a small number of molecules from a bulk solution. It traps molecules in nanofabricated chambers, or "dimples", and the trapped molecules are then studied on a fluorescence microscope at the single-molecule level. The sampling of bulk solution by dimples is representative, reproducible, and automated, enabling highthroughput single-molecule experiments. The device was applied to study hybridization of oligonucleotides, particularly in the context of reaction thermodynamics and kinetics in nanoconfinement. The DNA Pulley is a system to study protein binding and the local mechanical properties of DNA. A molecule of DNA is tethered to a surface on one end, and a superparamagnetic bead is attached to the other. A magnet pulls the DNA taut, and a silicon nitride knife with a nanoscale blade scans the DNA along its contour. Information on the local properties of the DNA is extracted by tracking the bead with nanometer precision in a white-light microscope. The system can detect proteins bound to DNA and localize their recognition sites, as shown with a model protein, EcoRI restriction enzyme. Progress on the measurements of nano-mechanical properties of DNA is included.

  14. Ultralong-range polyatomic Rydberg molecules

    NASA Astrophysics Data System (ADS)

    Gonzalez-Ferez, Rosario

    2016-05-01

    Ultralong-range polyatomic Rydberg molecules are formed when a ground-state atom is bound to a Rydberg atom. The binding mechanism of these Rydberg molecules is based on the low-energy collisions between a Rydberg electron and a ground-state atom and leads to the unusual oscillatory behavior of the adiabatic potential energy curves. If the ground-state atom immersed into the Rydberg wave function is replaced by a heteronuclear diatomic molecule another type of polyatomic Rydberg molecules can form. In this case, the Rydberg electron is coupled to the internal states of the polar ground-state molecule. In this talk, we will explore the electronic structure and rovibrational properties of these ultralong-range polyatomic Rydberg molecule. For the second type of Rydberg molecules, the polar dimer is allowed to rotate in the electric fields generated by the Rydberg electron and Rydberg core as well as an additional external field. We will investigate the metamorphosis of the Born-Oppenheimer potential curves, essential for the binding mechanism, with varying electric field and analyze the resulting properties such as the vibrational structure and the alignment and orientation of the polar dimer.

  15. Giant molecules composed of polar molecules and atoms in mixed dimensions

    NASA Astrophysics Data System (ADS)

    Qi, Ran; Tan, Shina

    2014-05-01

    Two or three polar molecules, confined to one or two dimensions, can form stable bound states with a single atom living in three dimensions, if the molecule and the atom can interact resonantly such that their mixed dimensional scattering length is large. We call these bound states ``giant molecules'' since it's a molecule composed of smaller molecules and atoms. We study their properties using techniques including exact numerical solution, exact qunatum diffusion Monte Carlo (QMC), Born-Oppenheimer approximation (BOA), and semiclassical approximation. These bound states have a hierarchical structure reminiscent of the celestial systems.

  16. Molecules-in-Molecules: An Extrapolated Fragment-Based Approach for Accurate Calculations on Large Molecules and Materials.

    PubMed

    Mayhall, Nicholas J; Raghavachari, Krishnan

    2011-05-10

    We present a new extrapolated fragment-based approach, termed molecules-in-molecules (MIM), for accurate energy calculations on large molecules. In this method, we use a multilevel partitioning approach coupled with electronic structure studies at multiple levels of theory to provide a hierarchical strategy for systematically improving the computed results. In particular, we use a generalized hybrid energy expression, similar in spirit to that in the popular ONIOM methodology, that can be combined easily with any fragmentation procedure. In the current work, we explore a MIM scheme which first partitions a molecule into nonoverlapping fragments and then recombines the interacting fragments to form overlapping subsystems. By including all interactions with a cheaper level of theory, the MIM approach is shown to significantly reduce the errors arising from a single level fragmentation procedure. We report the implementation of energies and gradients and the initial assessment of the MIM method using both biological and materials systems as test cases. PMID:26610128

  17. Line broadening of confined CO gas: from molecule-wall to molecule-molecule collisions with pressure.

    PubMed

    Hartmann, J-M; Boulet, C; Auwera, J Vander; El Hamzaoui, H; Capoen, B; Bouazaoui, M

    2014-02-14

    The infrared absorption in the fundamental band of CO gas confined in porous silica xerogel has been recorded at room temperature for pressures between about 5 and 920 hPa using a high resolution Fourier transform spectrometer. The widths of individual lines are determined from fits of measured spectra and compared with ab initio predictions obtained from requantized classical molecular dynamics simulations. Good agreement is obtained from the low pressure regime where the line shapes are governed by molecule-wall collisions to high pressures where the influence of molecule-molecule interactions dominates. These results, together with those obtained with a simple analytical model, indicate that both mechanisms contribute in a practically additive way to the observed linewidths. They also confirm that a single collision of a molecule with a wall changes its rotational state. These results are of interest for the determination of some characteristics of the opened porosity of porous materials through optical soundings. PMID:24527910

  18. Understanding Polymer Properties through Imaging of Molecules.

    NASA Astrophysics Data System (ADS)

    Sheiko, Sergei

    2008-03-01

    The unique advantage of Scanning Probe Microscopy (SPM) is that it allows imaging of flexible polymer molecules, whose overall size and local curvature are below the optical resolution limit. The role of molecular visualization has grown to be especially profound with the synthesis of complex macromolecules whose structure is difficult to confirm using conventional techniques such as NMR and light scattering. This is especially true for molecules that are branched, heterogeneous, and polydisperse. Here, SPM images provide unambiguous proof of the molecular architecture along with accurate analysis of size, conformation, and ordering of molecules on surfaces. The unique advantage of SPM is that one obtains molecular dimensions in direct space. This offers more opportunities for statistical analysis including fractionation of molecules by size, branching topology, and chemical composition as well as sorting out the irrelevant species. Unlike molecular characterization of static molecules, it remains challenging to study molecules as they move and react on surfaces. We will discuss pioneering AFM studies of flowing monolayers one molecule at a time. Through use of AFM, the flow process was monitored over a broad range of length scales from the millimeter long precursor film all the way down to the movements of individual molecules within the film. Molecular imaging enabled independent measurements both the driving and frictional forces that control spreading rate. In these studies, one also discovered a new type of flow instability in polymer monolayers caused by flow-induced conformational transitions. Recently, molecular imaging has been successfully used to monitor adsorption-induced degradation of branched molecules. These experiments open an entirely new perspective in chemistry wherein the chemical bonds can be mechanically activated upon the physical contact of a macromolecule with a substrate. This research directly impacts coatings, lubrication, heterogeneous

  19. Single molecule microscopy and spectroscopy: concluding remarks.

    PubMed

    van Hulst, Niek F

    2015-01-01

    Chemistry is all about molecules: control, synthesis, interaction and reaction of molecules. All too easily on a blackboard, one draws molecules, their structures and dynamics, to create an insightful picture. The dream is to see these molecules in reality. This is exactly what "Single Molecule Detection" provides: a look at molecules in action at ambient conditions; a breakthrough technology in chemistry, physics and biology. Within the realms of the Royal Society of Chemistry, the Faraday Discussion on "Single Molecule Microscopy and Spectroscopy" was a very appropriate topic for presentation, deliberation and debate. Undoubtedly, the Faraday Discussions have a splendid reputation in stimulating scientific debates along the traditions set by Michael Faraday. Interestingly, back in the 1830's, Faraday himself pursued an experiment that led to the idea that atoms in a compound were joined by an electrical component. He placed two opposite electrodes in a solution of water containing a dissolved compound, and observed that one of the elements of the compound accumulated on one electrode, while the other was deposited on the opposite electrode. Although Faraday was deeply opposed to atomism, he had to recognize that electrical forces were responsible for the joining of atoms. Probably a direct view on the atoms or molecules in his experiment would have convinced him. As such, Michael Faraday might have liked the gathering at Burlington House in September 2015 (). Surely, with the questioning eyes of his bust on the 1st floor corridor, the non-believer Michael Faraday has incited each passer-by to enter into discussion and search for deeper answers at the level of single molecules. In these concluding remarks, highlights of the presented papers and discussions are summarized, complemented by a conclusion on future perspectives. PMID:26606461

  20. Detecting high-density ultracold molecules using atom-molecule collision

    NASA Astrophysics Data System (ADS)

    Chen, Jun-Ren; Kao, Cheng-Yang; Chen, Hung-Bin; Liu, Yi-Wei

    2013-04-01

    Utilizing single-photon photoassociation, we have achieved ultracold rubidium molecules with a high number density that provides a new efficient approach toward molecular quantum degeneracy. A new detection mechanism for ultracold molecules utilizing inelastic atom-molecule collision is demonstrated. The resonant coupling effect on the formation of the X1Σ+g ground state 85Rb2 allows for a sufficient number of more deeply bound ultracold molecules, which induced an additional trap loss and heating of the co-existing atoms owing to the inelastic atom-molecule collision. Therefore, after the photoassociation process, the ultracold molecules can be investigated using the absorption image of the ultracold rubidium atoms mixed with the molecules in a crossed optical dipole trap. The existence of the ultracold molecules was then verified, and the amount of accumulated molecules was measured. This method detects the final produced ultracold molecules, and hence is distinct from the conventional trap loss experiment, which is used to study the association resonance. It is composed of measurements of the time evolution of an atomic cloud and a decay model, by which the number density of the ultracold 85Rb2 molecules in the optical trap was estimated to be >5.2 × 1011 cm-3.

  1. Phononic Molecules Studied by Raman Scattering

    SciTech Connect

    Lanzillotti-Kimura, N. D.; Fainstein, A.; Jusserand, B.; Lemaitre, A.

    2010-01-04

    An acoustic nanocavity can confine phonons in such a way that they act like electrons in an atom. By combining two of these phononic-atoms, it is possible to form a phononic 'molecule', with acoustic modes that are similar to the electronic states in a hydrogen molecule. We report Raman scattering experiments performed in a monolithic structure formed by a phononic molecule embedded in an optical cavity. The acoustic mode splitting becomes evident through both the amplification and change of selection rules induced by the optical cavity confinement. The results are in perfect agreement with photoelastic model simulations.

  2. Electron-impact-induced tryptophan molecule fragmentation

    NASA Astrophysics Data System (ADS)

    Tamuliene, Jelena; Romanova, Liudmila G.; Vukstich, Vasyl S.; Papp, Alexander V.; Snegursky, Alexander V.

    2015-01-01

    The fragmentation of a gas-phase tryptophan molecule by a low-energy (<70 eV) electron impact was studied both experimentally and theoretically. Various positively charged fragments were observed and analyzed. A special attention was paid to the energy characteristics of the ionic fragment yield. The geometrical parameters of the initial molecule rearrangement were also analyzed. The fragmentation observed was due to either a simple bond cleavage or more complex reactions involving molecular rearrangements. Contribution to the Topical Issue "Elementary Processes with Atoms and Molecules in Isolated and Aggregated States", edited by Friedrich Aumayr, Bratislav Marinkovic, Stefan Matejcik, John Tanis and Kurt H. Becker.

  3. H2 molecules and the intercloud medium

    NASA Technical Reports Server (NTRS)

    Hill, J. K.; Hollenbach, D. J.

    1976-01-01

    The paper discusses expected column densities of H2 in the intercloud medium and the possible use of molecules as indicators of intercloud physical conditions. Molecule formation by the H(-) process and on graphite grains is treated, and it is shown that the Barlow-Silk hypothesis of a 1-eV semichemical hydrogen-graphite bond leads to a large enhancement of the intercloud molecule-formation rate. Rotational-excitation calculations are presented for both cloud and intercloud conditions which show, in agreement with Jura (1975), that the presently observed optically thin H2 absorption components are more likely to originate in cold clouds than in the intercloud medium.

  4. Stereoelectronic switching in single-molecule junctions

    NASA Astrophysics Data System (ADS)

    Su, Timothy A.; Li, Haixing; Steigerwald, Michael L.; Venkataraman, Latha; Nuckolls, Colin

    2015-03-01

    A new intersection between reaction chemistry and electronic circuitry is emerging from the ultraminiaturization of electronic devices. Over decades chemists have developed a nuanced understanding of stereoelectronics to establish how the electronic properties of molecules relate to their conformation; the recent advent of single-molecule break-junction techniques provides the means to alter this conformation with a level of control previously unimagined. Here we unite these ideas by demonstrating the first single-molecule switch that operates through a stereoelectronic effect. We demonstrate this behaviour in permethyloligosilanes with methylthiomethyl electrode linkers. The strong σ conjugation in the oligosilane backbone couples the stereoelectronic properties of the sulfur-methylene σ bonds that terminate the molecule. Theoretical calculations support the existence of three distinct dihedral conformations that differ drastically in their electronic character. We can shift between these three species by simply lengthening or compressing the molecular junction, and, in doing so, we can switch conductance digitally between two states.

  5. Dynamics of molecules in extreme rotational states

    PubMed Central

    Yuan, Liwei; Teitelbaum, Samuel W.; Robinson, Allison; Mullin, Amy S.

    2011-01-01

    We have constructed an optical centrifuge with a pulse energy that is more than 2 orders of magnitude larger than previously reported instruments. This high pulse energy enables us to create large enough number densities of molecules in extreme rotational states to perform high-resolution state-resolved transient IR absorption measurements. Here we report the first studies of energy transfer dynamics involving molecules in extreme rotational states. In these studies, the optical centrifuge drives CO2 molecules into states with J ∼ 220 and we use transient IR probing to monitor the subsequent rotational, translational, and vibrational energy flow dynamics. The results reported here provide the first molecular insights into the relaxation of molecules with rotational energy that is comparable to that of a chemical bond.

  6. Synaptic Cell Adhesion Molecules in Alzheimer's Disease

    PubMed Central

    Leshchyns'ka, Iryna

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative brain disorder associated with the loss of synapses between neurons in the brain. Synaptic cell adhesion molecules are cell surface glycoproteins which are expressed at the synaptic plasma membranes of neurons. These proteins play key roles in formation and maintenance of synapses and regulation of synaptic plasticity. Genetic studies and biochemical analysis of the human brain tissue, cerebrospinal fluid, and sera from AD patients indicate that levels and function of synaptic cell adhesion molecules are affected in AD. Synaptic cell adhesion molecules interact with Aβ, a peptide accumulating in AD brains, which affects their expression and synaptic localization. Synaptic cell adhesion molecules also regulate the production of Aβ via interaction with the key enzymes involved in Aβ formation. Aβ-dependent changes in synaptic adhesion affect the function and integrity of synapses suggesting that alterations in synaptic adhesion play key roles in the disruption of neuronal networks in AD. PMID:27242933

  7. Single-Molecule Studies in Live Cells.

    PubMed

    Yu, Ji

    2016-05-27

    Live-cell single-molecule experiments are now widely used to study complex biological processes such as signal transduction, self-assembly, active trafficking, and gene regulation. These experiments' increased popularity results in part from rapid methodological developments that have significantly lowered the technical barriers to performing them. Another important advance is the development of novel statistical algorithms, which, by modeling the stochastic behaviors of single molecules, can be used to extract systemic parameters describing the in vivo biochemistry or super-resolution localization of biological molecules within their physiological environment. This review discusses recent advances in experimental and computational strategies for live-cell single-molecule studies, as well as a selected subset of biological studies that have utilized these new technologies. PMID:27070321

  8. Large molecules in diffuse interstellar clouds

    SciTech Connect

    Lepp, S.; Dalgarno, A.; Van Dishoeck, E.F.; Black, J.H.

    1988-06-01

    The effects of the presence of a substantial component of large molecules on the chemistry of diffuse molecular clouds are explored, and detailed models of the zeta Persei and zeta Ophiuchi clouds are constructed. The major consequence is a reduction in the abundances of singly charged atomic species. The long-standing discrepancy between cloud densities inferred from rotational and fine-structure level populations and from the ionization balance can be resolved by postulating a fractional abundance of large molecules of 1 x 10 to the -7th for zeta Persei and 6 x 10 to the -7th for zeta Ophiuchi. If the large molecules are polycyclic aromatic hydrocarbons (PAH) containing about 50 carbon atoms, they contain 1 percent of the carbon in zeta Persei and 7 percent in zeta Ophiuchi. Other consequences of the possible presence of PAH molecules are discussed. 23 references.

  9. Molecular junctions: Single-molecule contacts exposed

    NASA Astrophysics Data System (ADS)

    Nichols, Richard J.; Higgins, Simon J.

    2015-05-01

    Using a scanning tunnelling microscopy-based method it is now possible to get an atomistic-level description of the most probable binding and contact configuration for single-molecule electrical junctions.

  10. Stochastic Models of Molecule Formation on Dust

    NASA Technical Reports Server (NTRS)

    Charnley, Steven; Wirstroem, Eva

    2011-01-01

    We will present new theoretical models for the formation of molecules on dust. The growth of ice mantles and their layered structure is accounted for and compared directly to observations through simulation of the expected ice absorption spectra

  11. Macronuclear gene-sized molecules of hypotrichs.

    PubMed Central

    Hoffman, D C; Anderson, R C; DuBois, M L; Prescott, D M

    1995-01-01

    The macronuclear genome of hypotrichous ciliates consists of DNA molecules of gene-sized length. A macronuclear DNA molecule contains a single coding region. We have analyzed the many hypotrich macronuclear DNA sequences sequenced by us and others. No highly conserved promoter sequences nor replication initiation sequences have been identified in the 5' nor in the 3' non-translated regions, suggesting that promoter function in hypotrichs may differ from other eukaryotes. The macronuclear genes are intron-poor; approximately 19% of the genes sequenced to date have one to three introns. Not all macronuclear DNA molecules may be transcribed; some macronuclear molecules may not have any coding function. Codon bias in hypotrichs is different in many respects from other ciliates and from other eukaryotes. PMID:7753617

  12. Laser Spectroscopy of Atoms and Molecules.

    ERIC Educational Resources Information Center

    Schawlow, Arthur L.

    1978-01-01

    Surveys new laser techniques and a variety of spectroscopic experiments that can be used to detect, measure and study very small numbers of atoms on molecules. The range of applicability of these techniques is also included. (HM)

  13. Small Molecules from the Human Microbiota

    PubMed Central

    Donia, Mohamed S.; Fischbach, Michael A.

    2015-01-01

    Developments in the use of genomics to guide natural product discovery and a recent emphasis on understanding the molecular mechanisms of microbiota-host interactions have converged on the discovery of natural products from the human microbiome. Here, we review what is known about small molecules produced by the human microbiota. Numerous molecules representing each of the major metabolite classes have been found that have a variety of biological activities, including immune modulation and antibiosis. We discuss technologies that will affect how microbiota-derived molecules are discovered in the future, and consider the challenges inherent in finding specific molecules that are critical for driving microbe-host and microbe-microbe interactions and their biological relevance. PMID:26206939

  14. Biological mechanisms, one molecule at a time

    PubMed Central

    Tinoco, Ignacio; Gonzalez, Ruben L.

    2011-01-01

    The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome. PMID:21685361

  15. Single-Molecule Studies in Live Cells

    NASA Astrophysics Data System (ADS)

    Yu, Ji

    2016-05-01

    Live-cell single-molecule experiments are now widely used to study complex biological processes such as signal transduction, self-assembly, active trafficking, and gene regulation. These experiments' increased popularity results in part from rapid methodological developments that have significantly lowered the technical barriers to performing them. Another important advance is the development of novel statistical algorithms, which, by modeling the stochastic behaviors of single molecules, can be used to extract systemic parameters describing the in vivo biochemistry or super-resolution localization of biological molecules within their physiological environment. This review discusses recent advances in experimental and computational strategies for live-cell single-molecule studies, as well as a selected subset of biological studies that have utilized these new technologies.

  16. Water molecule conformation outside a metal surface

    NASA Astrophysics Data System (ADS)

    Flores, F.; Gabbay, I.; March, N. H.

    1981-05-01

    The effect of a metal surface on the conformation of a water molecule has been analyzed by discussing two independent effects: (i) the screening of the proton-proton repulsion, (ii) the interaction of the lone-pair orbitals with the surface. Both effects tend to increase the HOH angle. However, the interaction between the lone-pairs with the surface is the dominant effect for a water molecule approaching the surface. In particular, for a chemisorbed state this interaction is responsible for the major part of the molecule deformation. We have estimated that for H 2O chemisorbed on Ru, the HOH angle must increase from the free molecule value of 104.5° by 3.1 ± 0.5° in good agreement with the experimental evidence.

  17. Polyatomic molecules under intense femtosecond laser irradiation.

    PubMed

    Konar, Arkaprabha; Shu, Yinan; Lozovoy, Vadim V; Jackson, James E; Levine, Benjamin G; Dantus, Marcos

    2014-12-11

    Interaction of intense laser pulses with atoms and molecules is at the forefront of atomic, molecular, and optical physics. It is the gateway to powerful new tools that include above threshold ionization, high harmonic generation, electron diffraction, molecular tomography, and attosecond pulse generation. Intense laser pulses are ideal for probing and manipulating chemical bonding. Though the behavior of atoms in strong fields has been well studied, molecules under intense fields are not as well understood and current models have failed in certain important aspects. Molecules, as opposed to atoms, present confounding possibilities of nuclear and electronic motion upon excitation. The dynamics and fragmentation patterns in response to the laser field are structure sensitive; therefore, a molecule cannot simply be treated as a "bag of atoms" during field induced ionization. In this article we present a set of experiments and theoretical calculations exploring the behavior of a large collection of aryl alkyl ketones when irradiated with intense femtosecond pulses. Specifically, we consider to what extent molecules retain their molecular identity and properties under strong laser fields. Using time-of-flight mass spectrometry in conjunction with pump-probe techniques we study the dynamical behavior of these molecules, monitoring ion yield modulation caused by intramolecular motions post ionization. The set of molecules studied is further divided into smaller sets, sorted by type and position of functional groups. The pump-probe time-delay scans show that among positional isomers the variations in relative energies, which amount to only a few hundred millielectronvolts, influence the dynamical behavior of the molecules despite their having experienced such high fields (V/Å). High level ab initio quantum chemical calculations were performed to predict molecular dynamics along with single and multiphoton resonances in the neutral and ionic states. We propose the

  18. Protein mechanics: from single molecules to functional biomaterials.

    PubMed

    Li, Hongbin; Cao, Yi

    2010-10-19

    multidomain elastomeric proteins, and the design of novel elastomeric proteins that exhibit stimuli-responsive mechanical properties. Moving forward, we are now exploring the use of these artificial elastomeric proteins as building blocks of protein-based biomaterials. Ultimately, we would like to rationally tailor mechanical properties of elastomeric protein-based materials by programming the molecular sequence, and thus nanomechanical properties, of elastomeric proteins at the single-molecule level. This step would help bridge the gap between single protein mechanics and material biomechanics, revealing how the mechanical properties of individual elastomeric proteins are translated into the properties of macroscopic materials. PMID:20669937

  19. Modelling water molecules inside cyclic peptide nanotubes

    NASA Astrophysics Data System (ADS)

    Tiangtrong, Prangsai; Thamwattana, Ngamta; Baowan, Duangkamon

    2016-03-01

    Cyclic peptide nanotubes occur during the self-assembly process of cyclic peptides. Due to the ease of synthesis and ability to control the properties of outer surface and inner diameter by manipulating the functional side chains and the number of amino acids, cyclic peptide nanotubes have attracted much interest from many research areas. A potential application of peptide nanotubes is their use as artificial transmembrane channels for transporting ions, biomolecules and waters into cells. Here, we use the Lennard-Jones potential and a continuum approach to study the interaction of a water molecule in a cyclo[(- D-Ala- L-Ala)_4-] peptide nanotube. Assuming that each unit of a nanotube comprises an inner and an outer tube and that a water molecule is made up of a sphere of two hydrogen atoms uniformly distributed over its surface and a single oxygen atom at the centre, we determine analytically the interaction energy of the water molecule and the peptide nanotube. Using this energy, we find that, independent of the number of peptide units, the water molecule will be accepted inside the nanotube. Once inside the nanotube, we show that a water molecule prefers to be off-axis, closer to the surface of the inner nanotube. Furthermore, our study of two water molecules inside the peptide nanotube supports the finding that water molecules form an array of a 1-2-1-2 file inside peptide nanotubes. The theoretical study presented here can facilitate thorough understanding of the behaviour of water molecules inside peptide nanotubes for applications, such as artificial transmembrane channels.

  20. Vibrational spectroscopy of polar molecules with superradiance

    NASA Astrophysics Data System (ADS)

    Lin, Guin-Dar; Yelin, Susanne F.

    2013-07-01

    We investigate cooperative phenomena and superradiance for vibrational transitions in polar molecule spectroscopy of high optical-depth samples. Such cooperativity comes from the build-up of inter-particle coherence through dipole-dipole interactions and leads to speed-up of decay processes. We compare our calculation to recent work and find very good agreement, suggesting that superradiant effects need to be taken into account in a wide variety of ultracold molecule experiments, including vibrational and rotational states.

  1. Entropy bottlenecks in ion-molecule reactions

    NASA Technical Reports Server (NTRS)

    Dodd, J. A.; Brauman, J. I.; Golden, D. M.

    1984-01-01

    The significance of entropy bottlenecks in dissociation and recombination pathways in the prototype ionic system CH3 + CH3(+) has been investigated. Ion-molecule systems are shown to react through an entirely different dynamics than neutral systems, due to intrinsic differences in the shapes of the relevant potential surfaces. Consequences with regard to the interpretation of experimental rate parameters in the ion-molecule area are discussed.

  2. Do triatomic molecules echo atomic periodicity?

    SciTech Connect

    Hefferlin, R. Barrow, J.

    2015-03-30

    Demonstrations of periodicity among triatomic-molecular spectroscopic constants underscore the role of the periodic law as a foundation of chemistry. The objective of this work is to prepare for another test using vibration frequencies ν{sub 1} of free, ground-state, main-group triatomic molecules. Using data from four data bases and from computation, we have collected ν{sub 1} data for molecules formed from second period atoms.

  3. Spin-split states in aromatic molecules

    SciTech Connect

    Hirsh, J.E. . Dept. of Physics)

    1990-06-01

    A state where spin currents exist in the absence of external fields has recently been proposed to describe the low-temperature phase of chromium. It is proposed here that such a state may also describe the ground of aromatic molecules. It is argued that this point of view provides a more natural explanation for the large diamagnetic susceptibilities and NMR shifts observed in these molecules than the conventional viewpoint. The authors model suggests a new memory mechanism.

  4. Recovery of tritium from tritiated molecules

    DOEpatents

    Swansiger, W.A.

    1984-10-17

    This invention relates to the recovery of tritium from various tritiated molecules by reaction with uranium. More particularly, the invention relates to the recovery of tritium from tritiated molecules by reaction with uranium wherein the reaction is conducted in a reactor which permits the reaction to occur as a moving front reaction from the point where the tritium enters the reactor charged with uranium down the reactor until the uranium is exhausted.

  5. Feshbach molecules from an atomic Mott insulator

    NASA Astrophysics Data System (ADS)

    Volz, Thomas; Syassen, Niels; Bauer, Dominik; Hansis, Eberhard; Duerr, Stephan; Rempe, Gerhard

    2006-05-01

    Feshbach molecules from bosonic atomic species have proven to be very unstable with respect to inelastic collisions [1]. As a result, the typical lifetime observed for a cloud of ultracold ^87Rb2 molecules stored in an optical dipole trap is limited to a few ms.Here, we report on the observation of long-lived Feshbach molecules in an optical lattice. A BEC of ^87Rb atoms is loaded into the lowest Bloch band of a 3D optical lattice operated at a wavelength of 830 nm. By ramping up the lattice depth, the atomic gas enters the Mott insulator regime. A magnetic-field ramp through the Feshbach resonance at 1007 G creates molecules [2]. Lattice sites initially occupied with more than 2 atoms experience fast inelastic collisional losses. The observed lifetime of the remaining molecules is ˜100 ms, which is much longer than for a pure molecular sample in an optical dipole trap. Similar results have recently been reported in Ref.[3]. The increased lifetime is an important step on the route to a BEC of molecules in the vibrational ground state [4].[1] T. Mukaiyama et al., Phys. Rev. Lett. 92, 180402 (2004) [2] S. D"urr et al., Phys. Rev. Lett. 92, 020406 (2004) [3] G. Thalhammer et al., cond-mat/0510755 [4] D. Jaksch et al., Phys. Rev. Lett. 89, 040402 (2002)

  6. Sol-gel method for encapsulating molecules

    DOEpatents

    Brinker, C. Jeffrey; Ashley, Carol S.; Bhatia, Rimple; Singh, Anup K.

    2002-01-01

    A method for encapsulating organic molecules, and in particular, biomolecules using sol-gel chemistry. A silica sol is prepared from an aqueous alkali metal silicate solution, such as a mixture of silicon dioxide and sodium or potassium oxide in water. The pH is adjusted to a suitably low value to stabilize the sol by minimizing the rate of siloxane condensation, thereby allowing storage stability of the sol prior to gelation. The organic molecules, generally in solution, is then added with the organic molecules being encapsulated in the sol matrix. After aging, either a thin film can be prepared or a gel can be formed with the encapsulated molecules. Depending upon the acid used, pH, and other processing conditions, the gelation time can be from one minute up to several days. In the method of the present invention, no alcohols are generated as by-products during the sol-gel and encapsulation steps. The organic molecules can be added at any desired pH value, where the pH value is generally chosen to achieve the desired reactivity of the organic molecules. The method of the present invention thereby presents a sufficiently mild encapsulation method to retain a significant portion of the activity of the biomolecules, compared with the activity of the biomolecules in free solution.

  7. Quantum-classical lifetimes of Rydberg molecules

    NASA Astrophysics Data System (ADS)

    Junginger, Andrej; Main, Jörg; Wunner, Günter

    2013-04-01

    A remarkable property of Rydberg atoms is the possibility of creating molecules formed by one highly excited atom and another atom in the ground state. The first realization of such a Rydberg molecule has opened an active field of physical investigations, and showed that its basic properties can be described within a simple model regarding the ground state atom as a small perturber that is bound by a low-energy scattering process with the Rydberg electron (Greene et al 2000 Phys. Rev. Lett. 85 2458). Besides the good agreement between theory and the experiment concerning the vibrational states of the molecule, the experimental observations yield the astonishing feature that the lifetime of the molecule is clearly reduced as compared to the bare Rydberg atom (Butscher et al 2011 J. Phys. B: At. Mol. Opt. Phys. 44 184004). With focus on this yet unexplained observation, we investigate in this paper the vibrational ground state of the molecule in a quantum-classical framework. We show that the Rydberg wavefunction is continuously detuned by the presence of the moving ground state atom and that the timescale on which the detuning significantly exceeds the natural linewidth is in good agreement with the observed reduced lifetimes of the Rydberg molecule.

  8. Laser-Assisted Single Molecule Refolding

    NASA Astrophysics Data System (ADS)

    Zhao, Rui; Marshall, Myles; Aleman, Elvin; Lamichhane, Rajan; Rueda, David

    2010-03-01

    In vivo, many RNA molecules can adopt multiple conformations depending on their biological context such as the HIV Dimerization Initiation Sequence (DIS) or the DsrA RNA in bacteria. It is quite common that the initial interaction between the two RNAs takes place via complementary unpaired regions, thus forming a so-called kissing complex. However, the exact kinetic mechanism by which the two RNA molecules reach the dimerized state is still not well understood. To investigate the refolding energy surface of RNA molecules, we have developed new technology based on the combination of single molecule spectroscopy with laser induced temperature jump kinetics, called Laser Assisted Single-molecule Refolding (LASR). LASR enables us to induce folding reactions of otherwise kinetically trapped RNAs at the single molecule level, and to characterize their folding landscape. LASR provides an exciting new approach to study molecular memory effects and kinetically trapped RNAs in general. LASR should be readily applicable to study DNA and protein folding as well.

  9. Auxin biology revealed by small molecules.

    PubMed

    Ma, Qian; Robert, Stéphanie

    2014-05-01

    The plant hormone auxin regulates virtually every aspect of plant growth and development and unraveling its molecular and cellular modes of action is fundamental for plant biology research. Chemical genomics is the use of small molecules to modify protein functions. This approach currently rises as a powerful technology for basic research. Small compounds with auxin-like activities or affecting auxin-mediated biological processes have been widely used in auxin research. They can serve as a tool complementary to genetic and genomic methods, facilitating the identification of an array of components modulating auxin metabolism, transport and signaling. The employment of high-throughput screening technologies combined with informatics-based chemical design and organic chemical synthesis has since yielded many novel small molecules with more instantaneous, precise and specific functionalities. By applying those small molecules, novel molecular targets can be isolated to further understand and dissect auxin-related pathways and networks that otherwise are too complex to be elucidated only by gene-based methods. Here, we will review examples of recently characterized molecules used in auxin research, highlight the strategies of unraveling the mechanisms of these small molecules and discuss future perspectives of small molecule applications in auxin biology. PMID:24252105

  10. Single Molecule Raman Spectroscopy Under High Pressure

    NASA Astrophysics Data System (ADS)

    Fu, Yuanxi; Dlott, Dana

    2014-06-01

    Pressure effects on surface-enhanced Raman scattering spectra of Rhdoamine 6G adsorbed on silver nanoparticle surfaces was studied using a confocal Raman microscope. Colloidal silver nanoparticles were treated with Rhodamine 6G (R6G) and its isotopically substituted partner, R6G-d4. Mixed isotopomers let us identify single-molecule spectra, since multiple-molecule spectra would show vibrational transitions from both species. The nanoparticles were embedded into a poly vinyl alcohol film, and loaded into a diamond anvil cell for the high-pressure Raman scattering measurement. Argon was the pressure medium. Ambient pressure Raman scattering spectra showed few single-molecule spectra. At moderately high pressure ( 1GPa), a surprising effect was observed. The number of sites with observable spectra decreased dramatically, and most of the spectra that could be observed were due to single molecules. The effects of high pressure suppressed the multiple-molecule Raman sites, leaving only the single-molecule sites to be observed.

  11. Vibrational Cooling of Photoassociated Homonuclear Cold Molecules

    NASA Astrophysics Data System (ADS)

    Passagem, Henry; Ventura, Paulo; Tallant, Jonathan; Marcassa, Luis

    2015-05-01

    In this work, we produce vibrationally cold homonuclear Rb molecules using spontaneous optical pumping. The vibrationally cooled molecules are produced in three steps. In the first step, we use a photoassociation laser to produce molecules in high vibrational levels of the singlet ground state. Then in a second step, a 50 W broadband laser at 1071 nm, which bandwidth is about 2 nm, is used to transfer the molecules to lower vibrational levels via optical pumping through the excited state. This process transfers the molecules from vibrational levels around ν ~= 113 to a distribution of levels below ν = 35 . The molecules can be further cooled using a broadband light source near 685 nm. In order to obtain such broadband source, we have used a 5 mW superluminescent diode, which is amplified in a tapered amplifier using a double pass configuration. After the amplification, the spectrum is properly shaped and we end up with about 90 mW distributed in the 682-689 nm range. The final vibrational distribution is probed using resonance-enhanced multiphoton ionization with a pulsed dye laser near 670 nm operating at 4KHz. The results are presented and compared with theoretical simulations. This work was supported by Fapesp and INCT-IQ.

  12. Quantitative Aspects of Single Molecule Microscopy

    PubMed Central

    Ober, Raimund J.; Tahmasbi, Amir; Ram, Sripad; Lin, Zhiping; Ward, E. Sally

    2015-01-01

    Single molecule microscopy is a relatively new optical microscopy technique that allows the detection of individual molecules such as proteins in a cellular context. This technique has generated significant interest among biologists, biophysicists and biochemists, as it holds the promise to provide novel insights into subcellular processes and structures that otherwise cannot be gained through traditional experimental approaches. Single molecule experiments place stringent demands on experimental and algorithmic tools due to the low signal levels and the presence of significant extraneous noise sources. Consequently, this has necessitated the use of advanced statistical signal and image processing techniques for the design and analysis of single molecule experiments. In this tutorial paper, we provide an overview of single molecule microscopy from early works to current applications and challenges. Specific emphasis will be on the quantitative aspects of this imaging modality, in particular single molecule localization and resolvability, which will be discussed from an information theoretic perspective. We review the stochastic framework for image formation, different types of estimation techniques and expressions for the Fisher information matrix. We also discuss several open problems in the field that demand highly non-trivial signal processing algorithms. PMID:26167102

  13. Chapter 3: Small Molecules and Disease

    PubMed Central

    Wishart, David S.

    2012-01-01

    “Big” molecules such as proteins and genes still continue to capture the imagination of most biologists, biochemists and bioinformaticians. “Small” molecules, on the other hand, are the molecules that most biologists, biochemists and bioinformaticians prefer to ignore. However, it is becoming increasingly apparent that small molecules such as amino acids, lipids and sugars play a far more important role in all aspects of disease etiology and disease treatment than we realized. This particular chapter focuses on an emerging field of bioinformatics called “chemical bioinformatics” – a discipline that has evolved to help address the blended chemical and molecular biological needs of toxicogenomics, pharmacogenomics, metabolomics and systems biology. In the following pages we will cover several topics related to chemical bioinformatics. First, a brief overview of some of the most important or useful chemical bioinformatic resources will be given. Second, a more detailed overview will be given on those particular resources that allow researchers to connect small molecules to diseases. This section will focus on describing a number of recently developed databases or knowledgebases that explicitly relate small molecules – either as the treatment, symptom or cause – to disease. Finally a short discussion will be provided on newly emerging software tools that exploit these databases as a means to discover new biomarkers or even new treatments for disease. PMID:23300405

  14. Bipolar Conductance Switching of Single Anthradithiophene Molecules.

    PubMed

    Borca, Bogdana; Schendel, Verena; Pétuya, Rémi; Pentegov, Ivan; Michnowicz, Tomasz; Kraft, Ulrike; Klauk, Hagen; Arnau, Andrés; Wahl, Peter; Schlickum, Uta; Kern, Klaus

    2015-12-22

    Single molecular switches are basic device elements in organic electronics. The pentacene analogue anthradithiophene (ADT) shows a fully reversible binary switching between different adsorption conformations on a metallic surface accompanied by a charge transfer. These transitions are activated locally in single molecules in a low-temperature scanning tunneling microscope . The switching induces changes between bistable orbital structures and energy level alignment at the interface. The most stable geometry, the "off" state, which all molecules adopt upon evaporation, corresponds to a short adsorption distance at which the electronic interactions of the acene rings bend the central part of the molecule toward the surface accompanied by a significant charge transfer from the metallic surface to the ADT molecules. This leads to a shift of the lowest unoccupied molecular orbital down to the Fermi level (EF). In the "on" state the molecule has a flat geometry at a larger distance from the surface; consequently the interaction is weaker, resulting in a negligible charge transfer with an orbital structure resembling the highest occupied molecular orbital when imaged close to EF. The potential barrier between these two states can be overcome reversibly by injecting charge carriers locally into individual molecules. Voltage-controlled current traces show a hysteresis characteristic of a bipolar switching behavior. The interpretation is supported by first-principles calculations. PMID:26580569

  15. Nonlinear Dynamics of Atom-Molecule Conversion

    NASA Astrophysics Data System (ADS)

    Fu, Li-Bin; Liu, Jie

    2014-03-01

    The creation of ultracold molecules has opened up new possibilities for studies on molecular matter waves, strongly interacting superfluids, high-precision molecular spectroscopy and coherent molecular optics. In an atomic Bose-Einstein condensate (BEC) and a degenerate Fermi-Fermi or Fermi-Bose mixture, magnetic Feshbach resonance or optical photoassociation (PA) technique has been used to create not only diatomic molecules but also more complex molecules. In this chapter, we focus on many issues of nonlinear dynamics of atom-molecule systems. In Sec. 1, on the basis of the two-channelmean-field approach, we study the manybody effects on the Landau-Zener(LZ) picture of two-body molecular production through dramatically distorting the energy levels near the Feshbach resonance. In Sec. 2, we investigate the Feshbach resonance with modulation of an oscillating magnetic field. In Sec. 3, we include the nonlinear interparticle collisions and focus on the linear instability induced by the collisions and the adiabatic fidelity of the atom-trimer dark state in a stimulated Raman adiabatic passage (STIRAP). In Sec. 4, we theoretically investigate conversion problem from atom to N-body polyatomic molecule in an ultracold bosonic system by implementing the generalized STIRAP. In the last section, we discuss role of two-body interactions in the Feshbach conversion of fermionic atoms to bosonic molecules.

  16. Self-Assemblies of novel molecules, VECAR

    NASA Astrophysics Data System (ADS)

    Shrestha, Bijay; Kim, Hye-Young; Lee, Soojin; Novak, Brian; Moldovan, Dorel

    2015-03-01

    VECAR is a newly synthesized molecule, which is an amphiphilic antioxidant molecule that consists of two molecular groups, vitamin-E and Carnosine, linked by a hydrocarbon chain. The hydrocarbon chain is hydrophobic and both vitamin-E and Carnosine ends are hydrophilic. In the synthesis process, the length of the hydrophobic chain of VECAR molecules can vary from the shortest (n =0) to the longest (n =18), where n indicates the number of carbon atoms in the chain. We conducted MD simulation studies of self-assembly of VECAR molecules in water using GROMACS on LONI HPC resources. Our study shows that there is a strong correlation between the shape and atomistic structure of the self-assembled nano-structures (SANs) and the chain-length (n) of VECAR molecules. We will report the results of data analyses including the atomistic structure of each SANs and the dynamic and energetic mechanisms of their formation as function of time. In summary, both VECAR molecules of chain-length n =18 and 9 form worm-like micelles, which may be used as a drug delivery system. This research is supported by the Louisiana Board of Regents-RCS Grant (LEQSF(2012-15)-RD-A-19).

  17. Soft Landing of Complex Molecules on Surfaces

    SciTech Connect

    Johnson, Grant E.; Hu, Qichi; Laskin, Julia

    2011-07-01

    Mass spectrometry is a versatile technique for identification and structural characterization of large molecules. The advent of soft ionization techniques such as electrospray (ESI) (1-2) has enabled ionization of a wide variety of complex molecules without significant \\fragmentation while non-thermal ion sources such as laser vaporization (3-4) and magnetron sputtering (5-6) have provided access to materials that cannot, currently, be produced through conventional techniques. Most mass spectrometry studies rely on ionization of a molecule of interest or a complex mixture followed by mass analysis. Alternatively, mass spectrometry may be used as a preparatory technique, in which mass-selected ions are deposited onto solid supports or into liquid materials (7-18). Preparatory mass spectrometry offers several unique advantages for deposition of complex molecules on substrates including the ability to generate high-purity uniform films (19-20), unprecedented selectivity and specificity of preparation of deposited species (11, 21-22), the ability to focus and pattern an ion beam (23-24), and flexibility in both ion formation (1, 3, 25-26) and mass selection (27-32) processes. This review will highlight applications of mass-selected deposition of complex molecules for selective immobilization of biological molecules and catalytically active complexes on substrates.

  18. Small molecule TSHR agonists and antagonists.

    PubMed

    Neumann, S; Gershengorn, M C

    2011-04-01

    TSH activates the TSH receptor (TSHR) thereby stimulating the function of thyroid follicular cells (thyrocytes) leading to biosynthesis and secretion of thyroid hormones. Because TSHR is involved in several thyroid pathologies, there is a strong rationale for the design of small molecule "drug-like" ligands. Recombinant human TSH (rhTSH, Thyrogen(®)) has been used in the follow-up of patients with thyroid cancer to increase the sensitivity for detection of recurrence or metastasis. rhTSH is difficult to produce and must be administered by injection. A small molecule TSHR agonist could produce the same beneficial effects as rhTSH but with greater ease of oral administration. We developed a small molecule ligand that is a full agonist at TSHR. Importantly for its clinical potential, this agonist elevated serum thyroxine and stimulated thyroidal radioiodide uptake in mice after its absorption from the gastrointestinal tract following oral administration. Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate TSHR. We identified the first small molecule TSHR antagonists that inhibited TSH- and TSAb-stimulated signalling in primary cultures of human thyrocytes. Our results provide proof-of-principle for effectiveness of small molecule agonists and antagonists for TSHR. We suggest that these small molecule ligands are lead compounds for the development of higher potency ligands that can be used as probes of TSHR biology with therapeutic potential. PMID:21511239

  19. Single Molecule Conductance of Oligothiophene Derivatives

    NASA Astrophysics Data System (ADS)

    Dell, Emma J.

    This thesis studies the electronic properties of small organic molecules based on the thiophene motif. If we are to build next-generation devices, advanced materials must be designed which possess requisite electronic functionality. Molecules present attractive candidates for these ad- vanced materials since nanoscale devices are particularly sought after. However, selecting a molecule that is suited to a certain electronic function remains a challenge, and characterization of electronic behavior is therefore critical. Single molecule conductance measurements are a powerful tool to determine properties on the nanoscale and, as such, can be used to investigate novel building blocks that may fulfill the design requirements of next-generation devices. Combining these conductance results with strategic chemical synthesis allows for the development of new families of molecules that show attractive properties for future electronic devices. Since thiophene rings are the fruitflies of organic semiconductors on the bulk scale, they present an intriguing starting point for building functional materials on the nanoscale, and therefore form the structural basis of all molecules studied herein. First, the single-molecule conductance of a family of bithiophene derivatives was measured. A broad distribution in the single-molecule conductance of bithiophene was found compared with that of a biphenyl. This increased breadth in the conductance distribution was shown to be explained by the difference in 5-fold symmetry of thiophene rings as compared to the 6-fold symmetry of benzene rings. The reduced symmetry of thiophene rings results in a restriction on the torsion angle space available to these molecules when bound between two metal electrodes in a junction, causing each molecular junction to sample a different set of conformers in the conductance measurements. By contrast, the rotations of biphenyl are essentially unimpeded by junction binding, allowing each molecular junction

  20. Programing and Programed Instruction.

    ERIC Educational Resources Information Center

    Markle, Susan Meyer

    The impact of programed instruction on the educational system has been minimal quantitatively and qualitatively. In the interface between education and programing there are serious weaknesses in the design of materials, severe problems in the economics of design and use, and an almost insurmountable gulf between the philosophy or point of view on…

  1. Quantifying molecule-surface interactions using AFM-based single-molecule manipulation

    NASA Astrophysics Data System (ADS)

    Tautz, F. S.; Wagner, C.; Temirov, R.; Fournier, N.; Green, M.; Esat, T.; Leinen, P.; Groetsch, A.; Ruiz, V. G.; Tkatchenko, A.; Li, C.; Muellen, K.; Rohlfing, M.

    2015-03-01

    Scanning probe microscopy plays an important role in the investigation of molecular adsorption. Promising, is the possibility to probe the molecule-surface interaction while tuning its strength through AFM tip-induced single-molecule manipulation. Here, we outline a strategy to achieve quantitative understanding of such manipulation experiments. The example of qPlus sensor based PTCDA molecule lifting experiments is used to demonstrate how different aspects of the molecule-surface interaction, namely the short-range adsorption potential, the asymptotic van der Waals potential, local chemical bonds which are the source of the surface corrugation, and molecule-molecule interactions can be measured with SPM and interpreted by the help of force-field simulations.

  2. Current complexity: a tool for assessing the complexity of organic molecules.

    PubMed

    Li, Jun; Eastgate, Martin D

    2015-07-14

    Molecular complexity for a synthetic organic chemist is difficult to define, though intuitively known. Despite the importance of this concept, the quantitative assessment of complexity within organic chemistry has remained a challenge. We report here on the development of an approach for generating a unique complexity index, which is reflective of both intrinsic molecular complexity and extrinsic synthetic complexity. This index is based on a community's perception of complexity, within the context of current technology, calculating a molecule's current complexity. Our approach allows for a direct comparison between molecules, the analysis of trends within research programs, it enables an assessment (and comparison) of new synthetic approaches to known molecules and is capable of following a molecule's apparent complexity as it changes over time. PMID:25962620

  3. EGG Molecules Couple the Oocyte-to-Embryo Transition with Cell Cycle Progression

    PubMed Central

    Parry, Jean M.; Singson, Andrew

    2012-01-01

    The oocyte-to-embryo transition is a precisely coordinated process in which an oocyte become fertilized and transitions to an embryonic program of events. The molecules involved in this process have not been well studied. Recently a group of interacting molecules in C. elegans have been described as coordinating the oocyte-to-embryo transition with the advancement of the cell cycle. Genes egg-3, egg-4, and egg-5, represent a small class of regulatory molecules known as protein-tyrosine phosphase-like proteins, which can bind phosphorylated substrates and act as scaffolding molecules or inhibitors. These genes are responsible for coupling the movements and activities of regulatory kinase mbk-2 with advancement of the cell cycle during the oocyte-to-embryo transition. PMID:21630144

  4. Electromechanical Properties of Single Molecule Devices

    NASA Astrophysics Data System (ADS)

    Bruot, Christopher

    Understanding the interplay between the electrical and mechanical properties of single molecules is of fundamental importance for molecular electronics. The sensitivity of charge transport to mechanical fluctuations is a key problem in developing long lasting molecular devices. Furthermore, harnessing this response to mechanical perturbation, molecular devices which can be mechanically gated can be developed. This thesis demonstrates three examples of the unique electromechanical properties of single molecules. First, the electromechanical properties of 1,4-benzenedithiol molecular junctions are investigate. Counterintuitively, the conductance of this molecule is found to increase by more than an order of magnitude when stretched. This conductance increase is found to be reversible when the molecular junction is compressed. The current-voltage, conductance-voltage and inelastic electron tunneling spectroscopy characteristics are used to attribute the conductance increase to a strain-induced shift in the frontier molecular orbital relative to the electrode Fermi level, leading to resonant enhancement in the conductance. Next, the effect of stretching-induced structural changes on charge transport in DNA molecules is studied. The conductance of single DNA molecules with lengths varying from 6 to 26 base pairs is measured and found to follow a hopping transport mechanism. The conductance of DNA molecules is highly sensitive to mechanical stretching, showing an abrupt decrease in conductance at surprisingly short stretching distances, with weak dependence on DNA length. This abrupt conductance decrease is attributed to force-induced breaking of hydrogen bonds in the base pairs at the end of the DNA sequence. Finally, the effect of small mechanical modulation of the base separation on DNA conductance is investigated. The sensitivity of conductance to mechanical modulation is studied for molecules of different sequence and length. Sequences with purine-purine stacking

  5. Clusters of mobile molecules in supercooled water

    NASA Astrophysics Data System (ADS)

    Giovambattista, Nicolas; Buldyrev, Sergey V.; Stanley, H. Eugene; Starr, Francis W.

    2005-07-01

    We study the spatially heterogeneous dynamics in water via molecular dynamics simulations using the extended simple point charge potential. We identify clusters formed by mobile molecules and study their properties. We find that these clusters grow in size and become more compact as temperature decreases. We analyze the probability density function of cluster size, and we study the cluster correlation length. We find that clusters appear to be characterized by a fractal dimension consistent with that of lattice animals. We relate the cluster size and correlation length to the configurational entropy, Sconf . We find that these quantities depend weakly on 1/Sconf . In particular, the linearity found between the cluster mass n* and 1/Sconf suggests that n* may be interpreted as the mass of the cooperatively rearranging regions that form the basis of the Adam-Gibbs approach to the dynamics of supercooled liquids. We study the motion of molecules within a cluster, and find that each molecule preferentially follows a neighboring molecule in the same cluster. Based on this finding we hypothesize that stringlike cooperative motion may be a general mechanism for molecular rearrangement of complex, as well as simple liquids. By mapping each equilibrium configuration onto its corresponding local potential energy minimum or inherent structure (IS), we are able to compare the mobile molecule clusters in the equilibrium system with the molecules forming the clusters identified in the transitions between IS. We find that (i) mobile molecule clusters obtained by comparing different system configurations and (ii) clusters obtained by comparing the corresponding IS are completely different for short time scales, but are the same on the longer time scales of diffusive motion.

  6. Mining for Molecules in the Milky Way

    NASA Astrophysics Data System (ADS)

    2008-06-01

    Scientists are using the giant Robert C. Byrd Green Bank Telescope (GBT) to go prospecting in a rich molecular cloud in our Milky Way Galaxy. They seek to discover new, complex molecules in interstellar space that may be precursors to life. The GBT and Molecules The Robert C. Byrd Green Bank Telescope and some molecules it has discovered. CREDIT: Bill Saxton, NRAO/AUI/NSF "Clouds like this one are the raw material for new stars and planets. We know that complex chemistry builds prebiotic molecules in such clouds long before the stars and planets are formed. There is a good chance that some of these interstellar molecules may find their way to the surface of young planets such as the early Earth, and provide a head start for the chemistry of life. For the first time, we now have the capability to make a very thorough and methodical search to find all the chemicals in the clouds," said Anthony Remijan, of the National Radio Astronomy Observatory (NRAO). In the past three years, Remijan and his colleagues have used the GBT to discover ten new interstellar molecules, a feat unequalled in such a short time by any other team or telescope. The scientists discovered those molecules by looking specifically for them. However, they now are changing their strategy and casting a wide net designed to find whatever molecules are present, without knowing in advance what they'll find. In addition, they are making their data available freely to other scientists, in hopes of speeding the discovery process. The research team presented its plan to the American Astronomical Society's meeting in St. Louis, MO. As molecules rotate and vibrate, they emit radio waves at specific frequencies. Each molecule has a unique pattern of such frequencies, called spectral lines, that constitutes a "fingerprint" identifying that molecule. Laboratory tests can determine the pattern of spectral lines that identifies a specific molecule. Most past discoveries came from identifying a molecule's pattern in

  7. The reaction dynamics of alkali dimer molecules and electronically excited alkali atoms with simple molecules

    SciTech Connect

    Hou, H.

    1995-12-01

    This dissertation presents the results from the crossed molecular beam studies on the dynamics of bimolecular collisions in the gas phase. The primary subjects include the interactions of alkali dimer molecules with simple molecules, and the inelastic scattering of electronically excited alkali atoms with O2. The reaction of the sodium dimers with oxygen molecules is described in Chapter 2. Two reaction pathways were observed for this four-center molecule-molecule reaction, i.e. the formations of NaO2 + Na and NaO + NaO. NaO2 products exhibit a very anisotropic angular distribution, indicating a direct spectator stripping mechanism for this reaction channel. The NaO formation follows the bond breaking of O2, which is likely a result of a charge transfer from Na2 to the excited state orbital of O2-. The scattering of sodium dimers from ammonium and methanol produced novel molecules, NaNH3 and Na(CH3OH), respectively. These experimental observations, as well as the discussions on the reaction dynamics and the chemical bonding within these molecules, will be presented in Chapter 3. The lower limits for the bond dissociation energies of these molecules are also obtained. Finally, Chapter 4 describes the energy transfer between oxygen molecules and electronically excited sodium atoms.

  8. Theoretical Treatment of the Thermophysical Properties of Fluids Containing Chain-like Molecules

    SciTech Connect

    Carol K. Hall

    2008-11-14

    This research program was designed to enhance our understanding of the behavior of fluids and fluid mixtures containing chain-like molecules. The original objective was to explain and predict the experimentally observed thermophysical properties, including phase equilibria and dynamics, of systems containing long flexible molecules ranging in length from alkanes to polymers. Over the years the objectives were expanded to include the treatment of molecules that were not chain-like. Molecular dynamics and Monte Carlo computer simulations were used to investigate how variations in molecular size, shape and architecture influence the types of phase equilibria, thermodynamic properties, structure and surface interactions that are observed experimentally. The molecular insights and theories resulting from this program could eventually serve as the foundation upon which to build correlations of the properties of fluids that are both directly and indirectly related to the Nation’s energy resources including: petroleum, natural gas, and polymer solutions, melts, blends, and materials.

  9. SINGLE MOLECULE APPROACHES TO BIOLOGY, 2010 GORDON RESEARCH CONFERENCE, JUNE 27-JULY 2, 2010, ITALY

    SciTech Connect

    Professor William Moerner

    2010-07-09

    The 2010 Gordon Conference on Single-Molecule Approaches to Biology focuses on cutting-edge research in single-molecule science. Tremendous technical developments have made it possible to detect, identify, track, and manipulate single biomolecules in an ambient environment or even in a live cell. Single-molecule approaches have changed the way many biological problems are addressed, and new knowledge derived from these approaches continues to emerge. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of biomolecular machines: what they do, how they work individually, how they work together, and finally, how they work inside live cells. The burgeoning use of single-molecule methods to elucidate biological problems is a highly multidisciplinary pursuit, involving both force- and fluorescence-based methods, the most up-to-date advances in microscopy, innovative biological and chemical approaches, and nanotechnology tools. This conference seeks to bring together top experts in molecular and cell biology with innovators in the measurement and manipulation of single molecules, and will provide opportunities for junior scientists and graduate students to present their work in poster format and to exchange ideas with leaders in the field. A number of excellent poster presenters will be selected for short oral talks. Topics as diverse as single-molecule sequencing, DNA/RNA/protein interactions, folding machines, cellular biophysics, synthetic biology and bioengineering, force spectroscopy, new method developments, superresolution imaging in cells, and novel probes for single-molecule imaging will be on the program. Additionally, the collegial atmosphere of this Conference, with programmed discussion sessions as well as opportunities for informal gatherings in the afternoons and evenings in the beauty of the Il Ciocco site in

  10. Towards coherent control of ultracold molecule formation

    NASA Astrophysics Data System (ADS)

    Brown, Benjamin L.

    This thesis details experimental and theoretical investigations advancing the use of closed-loop coherent control for state-selective ultracold molecule formation in a magneto-optical trap (MOT). To date, no efficient scheme to produce a robust sample of ultracold (T ≤ 1 mK) molecules in arbitrarily-prescribed bound states has been demonstrated. The research presented here addresses this problem through the first experimental union of the fields of ultracold matter and ultrafast coherent control. A promising technique for producing ultracold molecules is to synthesize them directly from trapped ultracold atoms via photoassociation. This thesis explores a new extension of this approach: the application of closed-loop coherent control techniques employing broadband femtosecond optical pulses to enhance the efficiency and state-selectivity of photoassociative ultracold molecule formation. The experiments presented here studied the effects of chirped femtosecond pulses on the formation of ultracold triplet a3 S+u molecules in 85Rb and 87Rb MOTs. The application of femtosecond pulses suppressed, rather than increased, the formation of 85Rb2 and 87Rb2 a3 S+u molecules in contrast to comparable cw illumination and background formation rates. Positively chirped pulses were more efficient than non-chirped pulses of equivalent energy and spectral character at stimulating this quenching phenomenon. These results indicated that this suppression effect was coherent in nature, suggesting that coherent control is likely to be useful for manipulating the dynamics of ultracold quantum molecular gases. Time-dependent two-surface model simulations were performed to study several intuitive dynamical schemes employing femtosecond optical pulses to stimulate the formation of ground singlet X1 S+g molecules. These simulations focused on optical manipulation of the collision process at short-to-intermediate range (R < 50A), where stabilization of ultracold molecules to deeply bound

  11. Small Molecule Immunosensing Using Surface Plasmon Resonance

    PubMed Central

    Mitchell, John

    2010-01-01

    Surface plasmon resonance (SPR) biosensors utilize refractive index changes to sensitively detect mass changes at noble metal sensor surface interfaces. As such, they have been extensively applied to immunoassays of large molecules, where their high mass and use of sandwich immunoassay formats can result in excellent sensitivity. Small molecule immunosensing using SPR is more challenging. It requires antibodies or high-mass or noble metal labels to provide the required signal for ultrasensitive assays. Also, it can suffer from steric hindrance between the small antigen and large antibodies. However, new studies are increasingly meeting these and other challenges to offer highly sensitive small molecule immunosensor technologies through careful consideration of sensor interface design and signal enhancement. This review examines the application of SPR transduction technologies to small molecule immunoassays directed to different classes of small molecule antigens, including the steroid hormones, toxins, drugs and explosives residues. Also considered are the matrix effects resulting from measurement in chemically complex samples, the construction of stable sensor surfaces and the development of multiplexed assays capable of detecting several compounds at once. Assay design approaches are discussed and related to the sensitivities obtained. PMID:22163605

  12. Figuration and detection of single molecules

    NASA Astrophysics Data System (ADS)

    Nevels, R.; Welch, G. R.; Cremer, P. S.; Hemmer, P.; Phillips, T.; Scully, S.; Sokolov, A. V.; Svidzinsky, A. A.; Xia, H.; Zheltikov, A.; Scully, M. O.

    2012-08-01

    Recent advances in the description of atoms and molecules based on Dimensional scaling analysis, developed by Dudley Herschbach and co-workers, provided new insights into visualization of molecular structure and chemical bonding. Prof. Herschbach is also a giant in the field of single molecule scattering. We here report on the engineering of molecular detectors. Such systems have a wide range of application from medical diagnostics to the monitoring of chemical, biological and environmental hazards. We discuss ways to identify preselected molecules, in particular, mycotoxin contaminants using coherent laser spectroscopy. Mycotoxin contaminants, e.g. aflatoxin B1 which is present in corn and peanuts, are usually analysed by time-consuming microscopic, chemical and biological assays. We present a new approach that derives from recent experiments in which molecules are prepared by one (or more) femtosecond laser(s) and probed by another set. We call this technique FAST CARS (femto second adaptive spectroscopic technique for coherent anti-Stokes Raman spectroscopy). We propose and analyse ways in which FAST CARS can be used to identify preselected molecules, e.g. aflatoxin, rapidly and economically.

  13. The bound states of ultracold KRb molecules

    NASA Astrophysics Data System (ADS)

    Julienne, Paul; Hanna, Thomas

    2009-03-01

    Recently ultracold vibrational ground state ^40K^87Rb polar molecules have been made using magnetoassociation of two cold atoms to a weakly bound Feshbach molecule, followed by a two-color optical STIRAP process to transfer molecules to the molecular ground state [1]. We have used accurate potential energy curves for the singlet and triplet states of the KRb molecule [2] with coupled channels calculations to calculate all of the bound states of the ^40K^87Rb molecule as a function of magnetic field from the cold atom collision threshold to the v=0 ground state. We have also developed approximate models for understanding the changing properties of the molecular bound states as binding energy increases. Some overall conclusions from these calculations will be presented. [1] K.-K. Ni, S. Ospelkaus, M. H. G. de Miranda, A. Peer, B. Neyenhuis, J. J. Zirbel, S. Kotochigova, P. S. Julienne, D. S. Jin, and J. Ye, Science, 2008, 322, 231--235. [2] A. Pashov, O. Docenko, M. Tamanis, R. Ferber, H. Kn"ockel, and E. Tiemann, Phys. Rev. A, 2007, 76, 022511.

  14. Mining for Molecules in the Milky Way

    NASA Astrophysics Data System (ADS)

    2008-06-01

    Scientists are using the giant Robert C. Byrd Green Bank Telescope (GBT) to go prospecting in a rich molecular cloud in our Milky Way Galaxy. They seek to discover new, complex molecules in interstellar space that may be precursors to life. The GBT and Molecules The Robert C. Byrd Green Bank Telescope and some molecules it has discovered. CREDIT: Bill Saxton, NRAO/AUI/NSF "Clouds like this one are the raw material for new stars and planets. We know that complex chemistry builds prebiotic molecules in such clouds long before the stars and planets are formed. There is a good chance that some of these interstellar molecules may find their way to the surface of young planets such as the early Earth, and provide a head start for the chemistry of life. For the first time, we now have the capability to make a very thorough and methodical search to find all the chemicals in the clouds," said Anthony Remijan, of the National Radio Astronomy Observatory (NRAO). In the past three years, Remijan and his colleagues have used the GBT to discover ten new interstellar molecules, a feat unequalled in such a short time by any other team or telescope. The scientists discovered those molecules by looking specifically for them. However, they now are changing their strategy and casting a wide net designed to find whatever molecules are present, without knowing in advance what they'll find. In addition, they are making their data available freely to other scientists, in hopes of speeding the discovery process. The research team presented its plan to the American Astronomical Society's meeting in St. Louis, MO. As molecules rotate and vibrate, they emit radio waves at specific frequencies. Each molecule has a unique pattern of such frequencies, called spectral lines, that constitutes a "fingerprint" identifying that molecule. Laboratory tests can determine the pattern of spectral lines that identifies a specific molecule. Most past discoveries came from identifying a molecule's pattern in

  15. Modelling the spectroscopic behaviour of hot molecules

    NASA Astrophysics Data System (ADS)

    Tennyson, Jonathan

    2010-05-01

    At elevated temperatures the molecules absorb and emit light in a very complicated fashion which is hard to characterise on the basis of laboraroty measurement. Computed line lists of molecule transitions therefore provide a vital input for models of hot atmospheres. I will describe the calculation and use of such line lists including the BT2 water line list [1], which contains some 500 million distinct rotation-vibration transitions. This linelist proved crucial in the detection of water in extrasolar planet HD189733b and has been used extensively in atmospheric modelling. Illustrations will be given at the meeting. A new linelist for the ammonia molecule has just been completed [2] which shows that standard compilations for this molecule need to be improved. Progress on a more extensive linelist for hot ammonia and linelists for other molecules will be discussed at the meeting. [1] R.J. Barber, J. Tennyson, G.J. Harris and R.N. Tolchenov, Mon. Not. R. Astr. Soc., 368, 1087-1094 (2006) [2] S.N. Yurchenko, R.J. Barber, A. Yachmenev, W. Theil, P. Jensen and J. Tennyson, J. Phys. Chem. A, 113, 11845-11855 (2009).

  16. Assembling Ultracold Polar Molecules From Single Atoms

    NASA Astrophysics Data System (ADS)

    Liu, Lee R.; Hutzler, Nicholas R.; Yu, Yichao; Zhang, Jessie T.; Ni, Kang-Kuen

    2016-05-01

    Ultracold polar molecules are promising candidates for studying quantum many-body phenomena and building quantum information systems, due to their long-range, anisotropic, and tunable interactions. This calls for a technique to create low entropy samples of ultracold polar molecules with a large dipole moment. The lowest entropy molecular gas to date was created from atomic quantum gases in bulk or in optical lattices. The entropy is limited by that of the constituent atomic gases. We propose a method that addresses this limitation by assembling sodium cesium (NaCs) molecules from individually manipulated atoms. First, we load single Na and Cs atoms in separate optical tweezers from MOTs. We will cool them to their motional ground state using Raman sideband cooling and then merge them into a single tweezer. The tweezer confinement provides enhanced wavefunction overlap between the atom pair and molecule states. Using coherent two-photon techniques, we will then transfer the atom pair into a molecule. Our method offers reduced apparatus complexity and cycle time, single-site manipulation and imaging resolution, and should be readily extended to different species.

  17. Fluorescence Detection of Single DNA Molecules.

    PubMed

    Huang, Weidong; Wang, Yue; Wang, Zhimin

    2015-09-01

    Single-molecule detection (SMD) and single-molecule fluorescence resonance energy transfer (smFRET) were conducted using Cy3- and Cy5-labeled single-strand DNAs (ssDNAs) either immobilized on substrates or encapsulated in microdroplets. High-quality fluorescent images were obtained using a total internal reflection fluorescence microscope (TIRFM). In the substrate system, deposition of a low concentration of fluorescence molecules on substrates through electrostatic adsorption showed that most of the fluorescence spots were single molecules, and the mean value of signal to noise ratio (S/N) reached 6.9 ± 0.34. smFRET analysis was conducted through immobilization of donor- and acceptor-labeled oligonucleotides on substrates. In the droplet system, fluorophor-labeled oligonucleotides were injected into T-type microfluidics. Single and double fluorophor-labeled DNA molecules encapsulated in droplets were detected, the FRET efficiency and inter-dye distance of a single donor-acceptor pair were measured accurately. smFRET was conducted detailedly in the tortuous channel for the first time. PMID:26215080

  18. Ultracold molecules from the bottom-up

    NASA Astrophysics Data System (ADS)

    Zhang, Jessie T.; Hutzler, Nicholas R.; Liu, Lee R.; Yu, Yichao; Ni, Kang-Kuen

    2016-05-01

    Ultracold polar molecules exhibit strong, long-range, and tunable dipole-dipole interactions that may be utilized for a wide range of studies in quantum simulation and quantum information processing. To realize the full potential of these studies, it is desirable to have a low entropy sample of ultracold polar molecules with full control over both internal and external states, as well as inter-particle interactions. We work toward this goal with a new, bottom-up approach using the highly polar NaCs molecule. The key steps of our scheme are trapping single Na and Cs atoms in optical dipole traps, cooling the atoms to their motional ground state using Raman sideband cooling, and finally coherently transferring them to ground state NaCs molecules via a two-photon process. This approach should enable creation of low entropy samples with full control over all degrees of freedom, as well as realizing the possibility of single-site read-out and manipulation of molecules.

  19. Ultracold polar molecules near quantum degeneracy.

    PubMed

    Ospelkaus, S; Ni, K K; de Miranda, M H G; Neyenhuis, B; Wang, D; Kotochigova, S; Julienne, P S; Jin, D S; Ye, J

    2009-01-01

    We report the creation and characterization of a near quantum-degenerate gas of polar 40K-87Rb molecules in their absolute rovibrational ground state. Starting from weakly bound heteronuclear KRb Feshbach molecules, we implement precise control of the molecular electronic, vibrational, and rotational degrees of freedom with phase-coherent laser fields. In particular, we coherently transfer these weakly bound molecules across a 125 THz frequency gap in a single step into the absolute rovibrational ground state of the electronic ground potential. Phase coherence between lasers involved in the transfer process is ensured by referencing the lasers to two single components of a phase-stabilized optical frequency comb. Using these methods, we prepare a dense gas of 4 x 10(4) polar molecules at a temperature below 400 nK. This fermionic molecular ensemble is close to quantum degeneracy and can be characterized by a degeneracy parameter of T/T(F) = 3. We have measured the molecular polarizability in an optical dipole trap where the trap lifetime gives clues to interesting decay mechanisms. Given the large measured dipole moment of the KRb molecules of 0.5 Debye, the study of quantum degenerate molecular gases interacting via strong dipolar interactions is now within experimental reach. PACS numbers: 37.10.Mn, 37.10.Pq. PMID:20151553

  20. Molecules-to-Ecosphere View Emerges From Study of Student-Chosen Organisms

    ERIC Educational Resources Information Center

    Schmit, Palma J.

    1973-01-01

    Describes a high school biology program based on student investigations. The comparative study of different topics in plants and animals is stressed. First phase of the course centers around relationships between the ecosphere and the individual; the second phase considers the molecules and the individual. (PS)

  1. Sample preparation for single molecule localization microscopy.

    PubMed

    Allen, John R; Ross, Stephen T; Davidson, Michael W

    2013-11-21

    Single molecule localization-based optical nanoscopy was introduced in 2006, surpassing traditional diffraction-limited resolutions by an order of magnitude. Seven years later, this superresolution technique is continuing to follow a trend of increasing popularity and pervasiveness, with the proof-of-concept work long finished and commercial implementations now available. However one important aspect that tends to become lost in translation is the importance of proper sample preparation, with very few resources addressing the considerations that must be made when preparing samples for imaging with single molecule level sensitivity. Presented here is a an in-depth analysis of all aspects of sample preparation for single molecule superresolution, including both live and fixed cell preparation, choice of fluorophore, fixation and staining techniques, and imaging buffer considerations. PMID:24084850

  2. Complex molecules in the galactic center

    NASA Astrophysics Data System (ADS)

    Requena-Torres, Miguel Angel; Martin-Pintado, Jesus; Martin, Sergio; Amo-Baladron, Arancha

    2007-04-01

    Recently the number of complex organic molecules observed in hot cores has been increased by observing the Sgr B2N hot core, located in the GC molecular clouds. But in the inner 200pc of the center of our Galaxy complex organic molecules seems to widespread distributed along the Galactic plane. Last year large aldehydes where observed in the cm range with the Green Bank Telescope. These molecules where detected not in the hot core, but in the envelope of the SgrB2 molecular clouds and in two different positions in SgrA molecular cloud. We have not reach the maximum in the chemical complexity that these molecular clouds can show up. The next step would be to detect the more complex esters and ethers observed in hot cores and to obtain a better estimation of the physical conditions of the aldehydes observing more transitions in the mm range.

  3. Protein Scaffolding for Small Molecule Catalysts

    SciTech Connect

    Baker, David

    2014-09-14

    We aim to design hybrid catalysts for energy production and storage that combine the high specificity, affinity, and tunability of proteins with the potent chemical reactivities of small organometallic molecules. The widely used Rosetta and RosettaDesign methodologies will be extended to model novel protein / small molecule catalysts in which one or many small molecule active centers are supported and coordinated by protein scaffolding. The promise of such hybrid molecular systems will be demonstrated with the nickel-phosphine hydrogenase of DuBois et. al.We will enhance the hydrogenase activity of the catalyst by designing protein scaffolds that incorporate proton relays and systematically modulate the local environment of the catalyticcenter. In collaboration with DuBois and Shaw, the designs will be experimentally synthesized and characterized.

  4. Protein folding at single-molecule resolution

    PubMed Central

    Ferreon, Allan Chris M.; Deniz, Ashok A.

    2011-01-01

    The protein folding reaction carries great significance for cellular function and hence continues to be the research focus of a large interdisciplinary protein science community. Single-molecule methods are providing new and powerful tools for dissecting the mechanisms of this complex process by virtue of their ability to provide views of protein structure and dynamics without associated ensemble averaging. This review briefly introduces common FRET and force methods, and then explores several areas of protein folding where single-molecule experiments have yielded insights. These include exciting new information about folding landscapes, dynamics, intermediates, unfolded ensembles, intrinsically disordered proteins, assisted folding and biomechanical unfolding. Emerging and future work is expected to include advances in single-molecule techniques aimed at such investigations, and increasing work on more complex systems from both the physics and biology standpoints, including folding and dynamics of systems of interacting proteins and of proteins in cells and organisms. PMID:21303706

  5. Featured Molecules: Ascorbic Acid and Methylene Blue

    NASA Astrophysics Data System (ADS)

    Coleman, William F.; Wildman, Randall J.

    2003-05-01

    The WebWare molecules of the month for May are featured in several articles in this issue. "Arsenic: Not So Evil After All?" discusses the pharmaceutical uses of methylene blue and its development as the first synthetic drug used against a specific disease. The JCE Classroom Activity "Out of the Blue" and the article "Greening the Blue Bottle" feature methylene blue and ascorbic acid as two key ingredients in the formulation of the blue bottle. You can also see a colorful example of these two molecules in action on the cover. "Sailing on the 'C': A Vitamin Titration with a Twist" describes an experiment to determine the vitamin C (ascorbic acid) content of citrus fruits and challenges students, as eighteenth-century sea captains, to decide the best fruit to take on a long voyage. Fully manipulable (Chime) versions of these and other molecules are available at Only@JCE Online.

  6. X(3872) boson: Molecule or charmonium

    SciTech Connect

    Suzuki, Mahiko

    2005-12-01

    It has been argued that the mystery boson X(3872) is a molecule state consisting of primarily D{sup 0}D*{sup 0}+D{sup 0}D*{sup 0}. In contrast, apparent puzzles and potential difficulties have been pointed out for the charmonium assignment of X(3872). We examine several aspects of these alternatives by semiquantitative methods since quantitatively accurate results are often hard to reach on them. We point out that some of the observed properties of X(3872), in particular the binding and the production rates, are incompatible with the molecule interpretation. Despite puzzles and obstacles, X(3872) may fit more likely to the excited {sup 3}P{sub 1} charmonium than to the molecule after the mixing of cc with DD*+DD* is taken into account.

  7. Stochastic models for surface diffusion of molecules

    SciTech Connect

    Shea, Patrick Kreuzer, Hans Jürgen

    2014-07-28

    We derive a stochastic model for the surface diffusion of molecules, starting from the classical equations of motion for an N-atom molecule on a surface. The equation of motion becomes a generalized Langevin equation for the center of mass of the molecule, with a non-Markovian friction kernel. In the Markov approximation, a standard Langevin equation is recovered, and the effect of the molecular vibrations on the diffusion is seen to lead to an increase in the friction for center of mass motion. This effective friction has a simple form that depends on the curvature of the lowest energy diffusion path in the 3N-dimensional coordinate space. We also find that so long as the intramolecular forces are sufficiently strong, memory effects are usually not significant and the Markov approximation can be employed, resulting in a simple one-dimensional model that can account for the effect of the dynamics of the molecular vibrations on the diffusive motion.

  8. Difference Raman spectroscopy of DNA molecules

    NASA Astrophysics Data System (ADS)

    Anokhin, Andrey S.; Gorelik, Vladimir S.; Dovbeshko, Galina I.; Pyatyshev, Alexander Yu; Yuzyuk, Yury I.

    2015-01-01

    In this paper the micro-Raman spectra of calf DNA for different points of DNA sample have been recorded. The Raman spectra were made with help of difference Raman spectroscopy technique. Raman spectra were recorded with high spatial resolution from different points of the wet and dry samples in different spectral range (100÷4000cm-1) using two lasers: argon (514.5 nm) and helium -neon (632.8 nm). The significant differences in the Raman spectra for dry and wet DNA and for different points of DNA molecules were observed. The obtained data on difference Raman scattering spectra of DNA molecules may be used for identification of DNA types and for analysis of genetic information associated with the molecular structure of this molecule.

  9. Hydrogen sulfide and polysulfides as signaling molecules.

    PubMed

    Kimura, Hideo

    2015-01-01

    Hydrogen sulfide (H2S) is a familiar toxic gas that smells of rotten eggs. After the identification of endogenous H2S in the mammalian brain two decades ago, studies of this molecule uncovered physiological roles in processes such as neuromodulation, vascular tone regulation, cytoprotection against oxidative stress, angiogenesis, anti-inflammation, and oxygen sensing. Enzymes that produce H2S, such as cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase have been studied intensively and well characterized. Polysulfides, which have a higher number of inner sulfur atoms than that in H2S, were recently identified as potential signaling molecules that can activate ion channels, transcription factors, and tumor suppressors with greater potency than that of H2S. This article focuses on our contribution to the discovery of these molecules and their metabolic pathways and mechanisms of action. PMID:25864468

  10. T Cell Cosignaling Molecules in Transplantation.

    PubMed

    Ford, Mandy L

    2016-05-17

    The ultimate outcome of alloreactivity versus tolerance following transplantation is potently influenced by the constellation of cosignaling molecules expressed by immune cells during priming with alloantigen, and the net sum of costimulatory and coinhibitory signals transmitted via ligation of these molecules. Intense investigation over the last two decades has yielded a detailed understanding of the kinetics, cellular distribution, and intracellular signaling networks of cosignaling molecules such as the CD28, TNF, and TIM families of receptors in alloimmunity. More recent work has better defined the cellular and molecular mechanisms by which engagement of cosignaling networks serve to either dampen or augment alloimmunity. These findings will likely aid in the rational development of novel immunomodulatory strategies to prolong graft survival and improve outcomes following transplantation. PMID:27192567

  11. Prebiotically Important Molecules in Orion KL

    NASA Astrophysics Data System (ADS)

    Kuan, Yi-Jehng; Chuang, Yo-Ling

    Many interstellar, complex organic molecules are known to be prebiotically important and have essential functions in terrestrial biochemistry. Observations of complex organic molecular species in molecular clouds can thus enable us to test the origin of the primitive organic material found in the Solar System. Interstellar pyrimidine and glycine, the building block of nucleic acid and the simplest amino acid, respectively, are key molecules for astrobiology and were both detected in meteorites and comets. Although the formation of prebiotic molecules in extraterrestrial environments and their contribution to prebiotic chemistry and the origin of life remains unsettled, the connection between interstellar organic chemistry, meteoritic pyrimidines and amino acids, and the emergence of life on the early Earth would be strengthened with the discovery of interstellar pyrimidine and glycine. We have therefore observed the Orion KL hot molecular core to search for interstellar pyrimidine and for the confirmation of interstellar glycine using the ALMA array. We will present some of the encouraging, positive results.

  12. Hydrogen sulfide and polysulfides as signaling molecules

    PubMed Central

    KIMURA, Hideo

    2015-01-01

    Hydrogen sulfide (H2S) is a familiar toxic gas that smells of rotten eggs. After the identification of endogenous H2S in the mammalian brain two decades ago, studies of this molecule uncovered physiological roles in processes such as neuromodulation, vascular tone regulation, cytoprotection against oxidative stress, angiogenesis, anti-inflammation, and oxygen sensing. Enzymes that produce H2S, such as cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase have been studied intensively and well characterized. Polysulfides, which have a higher number of inner sulfur atoms than that in H2S, were recently identified as potential signaling molecules that can activate ion channels, transcription factors, and tumor suppressors with greater potency than that of H2S. This article focuses on our contribution to the discovery of these molecules and their metabolic pathways and mechanisms of action. PMID:25864468

  13. Ionization of glycerin molecule by electron impact

    NASA Astrophysics Data System (ADS)

    Zavilopulo, A. N.; Shpenik, O. B.; Markush, P. P.; Kontrosh, E. E.

    2015-07-01

    The methods and results of studying the yield of positive ions produced due to direct and dissociative electron impact ionization of the glycerin molecule are described. The experiment is carried out using two independent setups, namely, a setup with a monopole mass spectrometer employing the method of crossing electron and molecular beams and a setup with a hypocycloidal electron spectrometer with the gas-filled cell. The mass spectra of the glycerin molecule are studied in the range of mass numbers of 10-95 amu at various temperatures. The energy dependences of the effective cross sections of the glycerin molecular ions produced by a monoenergetic electron beam are obtained and analyzed; using these dependences, the appearance energies of fragment ions are determined. The dynamics of the glycerin molecule fragment ions formation is investigated in the temperature range of 300-340 K.

  14. Small Molecules in the Treatment of Psoriasis.

    PubMed

    Torres, Tiago; Filipe, Paulo

    2015-08-01

    Preclinical Research Psoriasis is an inflammatory systemic skin disease that affects various parts of the body requiring long-term management due to its chronic nature. Available treatment options include topical, systemic or biological therapies, which have long-term limitations associated to toxicity, tolerability and risk for adverse effects requiring its intermittent use and close monitoring. Small molecules modulate proinflammatory cytokines, selectively inhibit signaling pathways and showing potential to treat inflammatory diseases in patients not responding to conventional treatments. Presently, small molecules available are phosphodiesterase 4 inhibitors or Janus kinase inhibitors. Other small molecules under development for psoriasis include fumaric acid esters, amygdalin analogs, protein kinase C inhibitors, mitogen-activated protein kinase inhibitors, spleen protein kinase inhibitors, other tyrosine kinase inhibitors, sphingosine 1-phosphate receptor agonists, and A3 adenosine receptor agonists. These new treatment options represent important advances in the development of specific drugs to respond to the goals of treatment and improve patient quality of life. PMID:26255795

  15. Connexin channel permeability to cytoplasmic molecules.

    PubMed

    Harris, Andrew L

    2007-01-01

    Connexin channels are known to be permeable to a variety of cytoplasmic molecules. The first observation of second messenger junctional permeability, made approximately 30 years ago, sparked broad interest in gap junction channels as mediators of intercellular molecular signaling. Since then, much has been learned about the diversity of connexin channels with regard to isoform diversity, tissue and developmental distribution, modes of channel regulation, assembly, expression, biochemical modification and permeability, all of which appear to be dynamically regulated. This information has expanded the potential roles of connexin channels in development, physiology and disease, and made their elucidation much more complex--30 years ago such an orchestra of junctional dynamics was unanticipated. Only recently, however, have investigators been able to directly address, in this more complex framework, the key issue: what specific biological molecules, second messengers and others, are able to permeate the various types of connexin channels, and how well? An important related issue, given the ever-growing list of connexin-related pathologies, is how these permeabilities are altered by disease-causing connexin mutations. Together, many studies show that a variety of cytoplasmic molecules can permeate the different types of connexin channels. A few studies reveal differences in permeation by different molecules through a particular type of connexin channel, and differences in permeation by a particular molecule through different types of connexin channels. This article describes and evaluates the various methods used to obtain these data, presents an annotated compilation of the results, and discusses the findings in the context of what can be inferred about mechanism of selectivity and potential relevance to signaling. The data strongly suggest that highly specific interactions take place between connexin pores and specific biological molecular permeants, and that those

  16. Chiral Molecules Revisited by Broadband Microwave Spectroscopy

    NASA Astrophysics Data System (ADS)

    Schnell, Melanie

    2014-06-01

    Chiral molecules have fascinated chemists for more than 150 years. While their physical properties are to a very good approximation identical, the two enantiomers of a chiral molecule can have completely different (bio)chemical activities. For example, the right-handed enantiomer of carvone smells of spearmint while the left-handed one smells of caraway. In addition, the active components of many drugs are of one specific handedness, such as in the case of ibuprofen. However, in nature as well as in pharmaceutical applications, chiral molecules often exist in mixtures with other chiral molecules. The analysis of these complex mixtures to identify the molecular components, to determine which enantiomers are present, and to measure the enantiomeric excesses (ee) remains a challenging task for analytical chemistry, despite its importance for modern drug development. We present here a new method of differentiating enantiomers of chiral molecules in the gas phase based on broadband rotational spectroscopy. The phase of the acquired signal bares the signature of the enantiomer, as it depends upon the combined quantity, μ_a μ_b μ_c, which is of opposite sign between enantiomers. It thus also provides information on the absolute configuration of the particular enantiomer. Furthermore, the signal amplitude is proportional to the ee. A significant advantage of our technique is its inherent mixture compatibility due to the fingerprint-like character of rotational spectra. In this contribution, we will introduce the technique and present our latest results on chiral molecule spectroscopy and enantiomer differentiation. D. Patterson, M. Schnell, J.M. Doyle, Nature 497 (2013) 475-477 V.A. Shubert, D. Schmitz, D. Patterson, J.M. Doyle, M. Schnell, Angewandte Chemie International Edition 53 (2014) 1152-1155

  17. BCL::Conf: small molecule conformational sampling using a knowledge based rotamer library.

    PubMed

    Kothiwale, Sandeepkumar; Mendenhall, Jeffrey L; Meiler, Jens

    2015-01-01

    The interaction of a small molecule with a protein target depends on its ability to adopt a three-dimensional structure that is complementary. Therefore, complete and rapid prediction of the conformational space a small molecule can sample is critical for both structure- and ligand-based drug discovery algorithms such as small molecule docking or three-dimensional quantitative structure-activity relationships. Here we have derived a database of small molecule fragments frequently sampled in experimental structures within the Cambridge Structure Database and the Protein Data Bank. Likely conformations of these fragments are stored as 'rotamers' in analogy to amino acid side chain rotamer libraries used for rapid sampling of protein conformational space. Explicit fragments take into account correlations between multiple torsion bonds and effect of substituents on torsional profiles. A conformational ensemble for small molecules can then be generated by recombining fragment rotamers with a Monte Carlo search strategy. BCL::Conf was benchmarked against other conformer generator methods including Confgen, Moe, Omega and RDKit in its ability to recover experimentally determined protein bound conformations of small molecules, diversity of conformational ensembles, and sampling rate. BCL::Conf recovers at least one conformation with a root mean square deviation of 2 Å or better to the experimental structure for 99 % of the small molecules in the Vernalis benchmark dataset. The 'rotamer' approach will allow integration of BCL::Conf into respective computational biology programs such as Rosetta.Graphical abstract:Conformation sampling is carried out using explicit fragment conformations derived from crystallographic structure databases. Molecules from the database are decomposed into fragments and most likely conformations/rotamers are used to sample correspondng sub-structure of a molecule of interest. PMID:26473018

  18. Modeling single-molecule detection statistics

    NASA Astrophysics Data System (ADS)

    Enderlein, Joerg; Robbins, David L.; Ambrose, W. P.; Goodwin, Peter M.; Keller, Richard A.

    1997-05-01

    We present experimental results of single B-phycoerythrin molecule detection in a fluid flow at different sample introduction rates. A new mathematical approach is used for calculating the resulting burst size distributions. The calculations are based upon a complete physical model including absorption, fluorescence and photobleaching characteristics of the fluorophore; its diffusion; the sample stream hydrodynamics; the spatially dependent optical detection efficiency; and the excitation laser beam characteristics. Special attention is paid to the phenomenon of `molecular noise'--fluctuations in the number of overlapping crossings of molecules through the detection volume. The importance of this study and its connections to experimental applications are discussed.

  19. COCIS: Markov processes in single molecule fluorescence

    PubMed Central

    Talaga, David S.

    2009-01-01

    This article examines the current status of Markov processes in single molecule fluorescence. For molecular dynamics to be described by a Markov process, the Markov process must include all states involved in the dynamics and the FPT distributions out of those states must be describable by a simple exponential law. The observation of non-exponential first-passage time distributions or other evidence of non-Markovian dynamics is common in single molecule studies and offers an opportunity to expand the Markov model to include new dynamics or states that improve understanding of the system. PMID:19543444

  20. Formation and analysis of ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Juarros, Elizabeth Ann

    Alkali hydride molecules are polar, exhibiting large ground-state dipole moments. As ultracold sources of alkali atoms, as well as hydrogen, have been created in the laboratory, we explore theoretically the feasibility of forming such molecules from a mixture of the ultracold atomic gases, employing various photoassociation schemes. In this work we use lithium and sodium hydride as benchmark systems to calculate molecule formation rates through stimulated one-photon radiative association directly from the continuum as well as two-photon stimulated radiative association (Raman transfer) and excitation to bound levels of an excited state followed by spontaneous emission to the ground state. Using accurate molecular potential energy curves and dipole transition moments and with laser intensities and MOT densities that are easily attainable experimentally, we have found that substantial molecule formation rates can be realized even after the effect of back-stimulation has been accounted for. We examine the spontaneous emission cascade which takes place from the upper vibrational levels of the singlet ground state on a time scale of milliseconds. Because photon emission in the cascade process does not contribute to trap loss, a sizable population of molecules in the lowest vibrational level can be achieved. The triplet ground electronic state is of particular interest for experimental efforts since, although it has never been observed experimentally, molecular structure calculations of the a3Sigma+ state for LiH and NaH predict a small van der Waals attraction, with a potential energy well so shallow that it can support only one bound rotational-vibrational level. Any molecule formed in the triplet ground state would then be immediately in the lowest and most stable level of that state and would be quite long-lived, unlike molecules in high vibrational levels which have significantly shorter lifetimes. As an analysis of our method of calculating molecule formation rates

  1. Manipulation of molecules with electric fields

    NASA Astrophysics Data System (ADS)

    Meijer, Gerard

    2004-05-01

    During the last few years we have been experimentally exploring the possibilities of manipulating neutral polar molecules with electric fields [1]. Arrays of time-varying, inhomogeneous electric fields have been used to reduce in a stepwise fashion the forward velocity of molecules in a beam. With this so-called 'Stark-decelerator', the equivalent of a LINear ACcelerator (LINAC) for charged particles, one can transfer the high phase-space density that is present in the moving frame of a pulsed molecular beam to a reference frame at any desired velocity; molecular beams with a computer-controlled (calibrated) velocity and with a narrow velocity distribution, corresponding to sub-mK longitudinal temperatures, can be produced. These decelerated beams offer new possibilities for collision studies, for instance, and enable spectroscopic studies with an improved spectral resolution; first proof-of-principle high-resolution spectroscopic studies have been performed. These decelerated beams have also been used to load neutral ammonia molecules in an electrostatic trap at a density of (better than) 10^7 mol/cm^3 and at temperatures of around 25 mK. In another experiment, a decelerated beam of ammonia molecules is injected in an electrostatic storage ring. The package of molecules in the ring can be observed for more than 50 distinct round trips, corresponding to 40 meter in circular orbit and almost 0.5 sec. storage time, sufficiently long for a first investigation of its transversal motion in the ring. A scaled up version of the Stark-decelerator and molecular beam machine has just become operational, and has been used to produce decelerated beams of ground-state OH and electronically excited (metastable) NH radicals. The NH radical is particularly interesting, as an optical pumping scheme enables the accumulation of decelerated bunches of slow NH molecules, either in a magnetic or in an optical trap. By miniaturizing the electrode geometries, high electric fields can be

  2. The origin of life. [genetically important molecules

    NASA Technical Reports Server (NTRS)

    Horowitz, N. H.; Hubbard, J. S.

    1974-01-01

    Research in the areas of precambrian paleontology, chemical evolution of genetically important monomers, prebiotic dehydration-condensation reactions, organic compounds in meteorites and interstellar space, and biological exploration of the planets is summarized. Fossils in precambrian cherts and findings of eukaryotic cells are described, and recent investigations of prebiotic conditions, energy sources, and starting materials for genetic molecules are outlined. Studies of homogeneous and heterogeneous dehydrations and of nonaqueous thermal dehydrations are described. The detection of amino acids, purines, and pyrimidines in meteorites and of biologically significant molecules in interstellar clouds is discussed, as well as the possibilities of life on Jupiter, Mars, and Titan.

  3. Dissociation of ultracold molecules with Feshbach resonances

    SciTech Connect

    Duerr, Stephan; Volz, Thomas; Rempe, Gerhard

    2004-09-01

    Ultracold molecules are associated from an atomic Bose-Einstein condensate by ramping a magnetic field across a Feshbach resonance. The reverse ramp dissociates the molecules. The kinetic energy released in the dissociation process is used to measure the widths of four Feshbach resonances in {sup 87}Rb. This method to determine the width works remarkably well for narrow resonances even in the presence of significant magnetic-field noise. In addition, a quasimonoenergetic atomic wave is created by jumping the magnetic field across the Feshbach resonance.

  4. Optical Production of Ultracold Polar Molecules

    SciTech Connect

    Sage, Jeremy M.; Sainis, Sunil; DeMille, David; Bergeman, Thomas

    2005-05-27

    We demonstrate the production of ultracold polar RbCs molecules in their vibronic ground state, via photoassociation of laser-cooled atoms followed by a laser-stimulated state transfer process. The resulting sample of X{sup 1}{sigma}{sup +}(v=0) molecules has a translational temperature of {approx}100 {mu}K and a narrow distribution of rotational states. With the method described here it should be possible to produce samples even colder in all degrees of freedom, as well as other bialkali species.

  5. Electrostatic propulsion using C60 molecules

    NASA Technical Reports Server (NTRS)

    Leifer, Stephanie D.; Rapp, Donald; Saunders, Winston A.

    1992-01-01

    An evaluation is made of the potential benefits of C60 molecules as a basis for ion propulsion. Because C60 is storable, its use may result in a larger usable propellant fraction than previous methods of cluster ion propulsion. C60 may also relax such engineering constraints as grid spacing, which restrict the performance of noble gas ion propulsion. The behavior of C60 in a plasma discharge environment, as well as various electron impact cross sections of the molecule, will greatly afftect the feasibility of the concept.

  6. Single-molecule electrophoresis. Final report

    SciTech Connect

    Castro, A.; Shera, E.B.

    1996-05-22

    A novel method for the detection and identification of single molecules in solution has been devised, computer-simulated, and experimentally achieved. The technique involves the determination of electrophoretic velocities by measuring the time required by individual molecules to travel a fixed distance between two laser beams. Computer simulations of the process were performed beforehand in order to estimate the experimental feasibility of the method, and to determine the optimum values for the various experimental parameters. Examples of the use of the technique for the ultrasensitive detection and identification of rhodamine-6G, a mixture of DNA restriction fragments, and a mixture of proteins in aqueous solution are presented.

  7. The Interactions Between Nitrogen and Oxygen Molecules

    NASA Technical Reports Server (NTRS)

    Meador, Willard E., Jr.

    1960-01-01

    Lippincott's delta-function model for atomic interactions is analyzed, both physically and mathematically, and extended, by differentiation between K- and L-shell electrons and the introduction of a variable parameter in the expression for the delta-function strength, to cover homonuclear molecules more complex than hydrogen. In addition, modifications are made which allow treatments of diatomic, heteronuclear molecules. This theory, in conjunction with a reasonably extensive study of resonance, dispersion, and configuration interaction phenomena, as well as the use of simple quantum mechanical arguments, is then applied to the N2-N2, N2-O2, and O2-O2 interactions.

  8. Molecules and Clusters in Intense Laser Fields

    NASA Astrophysics Data System (ADS)

    Posthumus, Jan

    2009-09-01

    Preface; 1. Ultra-high intensity based on Ti:Sapphire Philip F. Taday and Andrew J. Langley; 2. Diatomic molecules in intense laser fields Jan H. Posthumus and James F. McCann; 3. Small polyatomic molecules in intense laser fields C. Cornaggia; 4. Coherent control in intense laser fields Eric Charron and Brian Sheehy; 5. Experimental studies of laser-heated rare gas clusters M. Lezius and M. Schmidt; 6. Single cluster explosions and high harmonic generation John W. G. Tisch and Emma Springate; 7. Intense laser interaction with extended cluster media Roland A. Smith and Todd Ditmire.

  9. Molecules and Clusters in Intense Laser Fields

    NASA Astrophysics Data System (ADS)

    Posthumus, Jan

    2001-06-01

    Preface; 1. Ultra-high intensity based on Ti:Sapphire Philip F. Taday and Andrew J. Langley; 2. Diatomic molecules in intense laser fields Jan H. Posthumus and James F. McCann; 3. Small polyatomic molecules in intense laser fields C. Cornaggia; 4. Coherent control in intense laser fields Eric Charron and Brian Sheehy; 5. Experimental studies of laser-heated rare gas clusters M. Lezius and M. Schmidt; 6. Single cluster explosions and high harmonic generation John W. G. Tisch and Emma Springate; 7. Intense laser interaction with extended cluster media Roland A. Smith and Todd Ditmire.

  10. Synthesis of biological molecules on molecular sieves.

    PubMed

    Poncelet, G; Van Assche, A T; Fripiat, J J

    1975-07-01

    Catalytic properties of aluminosilicates may play a role in the synthesis of biological molecules from simple gaseous molecules commonly found in planetary atmospheres. Urea, amino acids and UV absorbing substances have been obtained by heating CO and NH3 with Linde molecular sieves saturated with Ca+2, NH4+ or Fe+3. The yields of amino acids produced have been determined by an amino acid analyzer. The quantity of urea produced largely depends on the nature of the saturating cation. Experiments using 14CO confirm that the amino acids are not due to contaminants adsorbed on the surface of the molecular sieves. PMID:171609

  11. Design of small-molecule epigenetic modulators

    PubMed Central

    Pachaiyappan, Boobalan

    2013-01-01

    The field of epigenetics has expanded rapidly to reveal multiple new targets for drug discovery. The functional elements of the epigenomic machinery can be catagorized as writers, erasers and readers, and together these elements control cellular gene expression and homeostasis. It is increasingly clear that aberrations in the epigenome can underly a variety of diseases, and thus discovery of small molecules that modulate the epigenome in a specific manner is a viable approach to the discovery of new therapeutic agents. In this Digest, the components of epigenetic control of gene expression will be briefly summarized, and efforts to identify small molecules that modulate epigenetic processes will be described. PMID:24300735

  12. Newly detected molecules in dense interstellar clouds

    NASA Technical Reports Server (NTRS)

    Irvine, William M.; Ziurys, L. M.; Avery, L. W.; Matthews, H. E.; Friberg, P.

    1988-01-01

    The last year or so has seen the identification of several new interstellar molecules, including C2S, C3S, C5H, C6H, and (probably) HC2CHO in the cold, dark cloud TMC-1, and the discovery of the first interstellar phosphorus-containing molecule, PN, in the Orion 'plateau' source. Further interesting results include the observations of (C-13))3H2 and C3HD, and the first detection of HCOOH (formic acid) in a (C-13)3H2 cold cloud.

  13. Adhesion molecules in inflammatory bowel disease.

    PubMed Central

    Jones, S C; Banks, R E; Haidar, A; Gearing, A J; Hemingway, I K; Ibbotson, S H; Dixon, M F; Axon, A T

    1995-01-01

    The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), E selectin, and vascular cell adhesion molecule 1 (VCAM-1) were studied in the serum of patients with Crohn's disease, ulcerative colitis, and healthy controls. A second blood sample was taken from patients with active disease after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating VCAM-1 concentrations were significantly higher in patients with active ulcerative colitis (n = 11, median = 165 U/ml) compared with patients with inactive ulcerative colitis (n = 10, median = 117 U/ml, p < 0.005), active Crohn's disease (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in E selectin or ICAM-1 concentrations between the active and inactive states, however, patients with active Crohn's disease had significantly higher ICAM-1 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). VCAM-1 concentrations fell significantly from pretreatment values to remission in active ulcerative colitis (p < 0.01). In Crohn's disease there was a significant fall in ICAM-1 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of ICAM-1 occurred more often and was more intense in inflamed tissue sections from patients with ulcerative colitis and Crohn's disease than from controls. Vascular labelling with antibody to E selectin also occurred more often in patients with active inflammatory bowel disease. In conclusion, increased circulating concentrations of selected adhesion molecules are associated with

  14. Oncogenic protein interfaces: small molecules, big challenges.

    PubMed

    Nero, Tracy L; Morton, Craig J; Holien, Jessica K; Wielens, Jerome; Parker, Michael W

    2014-04-01

    Historically, targeting protein-protein interactions with small molecules was not thought possible because the corresponding interfaces were considered mostly flat and featureless and therefore 'undruggable'. Instead, such interactions were targeted with larger molecules, such as peptides and antibodies. However, the past decade has seen encouraging breakthroughs through the refinement of existing techniques and the development of new ones, together with the identification and exploitation of unexpected aspects of protein-protein interaction surfaces. In this Review, we describe some of the latest techniques to discover modulators of protein-protein interactions and how current drug discovery approaches have been adapted to successfully target these interfaces. PMID:24622521

  15. Accurate density functional thermochemistry for larger molecules.

    SciTech Connect

    Raghavachari, K.; Stefanov, B. B.; Curtiss, L. A.; Lucent Tech.

    1997-06-20

    Density functional methods are combined with isodesmic bond separation reaction energies to yield accurate thermochemistry for larger molecules. Seven different density functionals are assessed for the evaluation of heats of formation, Delta H 0 (298 K), for a test set of 40 molecules composed of H, C, O and N. The use of bond separation energies results in a dramatic improvement in the accuracy of all the density functionals. The B3-LYP functional has the smallest mean absolute deviation from experiment (1.5 kcal mol/f).

  16. Making More-Complex Molecules Using Superthermal Atom/Molecule Collisions

    NASA Technical Reports Server (NTRS)

    Shortt, Brian; Chutjian, Ara; Orient, Otto

    2008-01-01

    A method of making more-complex molecules from simpler ones has emerged as a by-product of an experimental study in outer-space atom/surface collision physics. The subject of the study was the formation of CO2 molecules as a result of impingement of O atoms at controlled kinetic energies upon cold surfaces onto which CO molecules had been adsorbed. In this study, the O/CO system served as a laboratory model, not only for the formation of CO2 but also for the formation of other compounds through impingement of rapidly moving atoms upon molecules adsorbed on such cold interstellar surfaces as those of dust grains or comets. By contributing to the formation of increasingly complex molecules, including organic ones, this study and related other studies may eventually contribute to understanding of the origins of life.

  17. Phase imaging of moving DNA molecules and DNA molecules replicated in the atomic force microscope.

    PubMed Central

    Argaman, M; Golan, R; Thomson, N H; Hansma, H G

    1997-01-01

    Phase imaging with a tapping mode atomic force microscope (AFM) has many advantages for imaging moving DNA and DNA-enzyme complexes in aqueous buffers at molecular resolution. In phase images molecules can be resolved at higher scan rates and lower forces than in height images from the AFM. Higher scan rates make it possible to image faster processes. At lower forces the molecules are imaged more gently. Moving DNA molecules are also resolved more clearly in phase images than in height images. Phase images in tapping mode AFM show the phase difference between oscillation of the piezoelectric crystal that drives the cantilever and oscillation of the cantilever as it interacts with the sample surface. Phase images presented here show moving DNA molecules that have been replicated with Sequenase in the AFM and DNA molecules tethered in complexes with Escherichia coli RNA polymerase. PMID:9336471

  18. Small diatomic alkali molecules at ultracold temperatures

    NASA Astrophysics Data System (ADS)

    Wang, Tout Taotao

    This thesis describes experimental work done with two of the smallest diatomic alkali molecules, 6Li2 and 23Na 6Li, each formed out of its constituent atoms at ultracold temperatures. The 23Na6Li molecule was formed for the first time at ultracold temperatures, after previous attempts failed due to an incorrect assignment of Feshbach resonances in the 6Li+23Na system. The experiment represents successful molecule formation around the most difficult Feshbach resonance ever used, and opens up the possibility of transferring NaLi to its spin-triplet ground state, which has both magnetic and electric dipole moments and is expected to be long-lived. For 6Li2, the experimental efforts in this thesis have solved a long-standing puzzle of apparently long lifetimes of closed-channel fermion pairs around a narrow Feshbach resonance, finding that the lifetime is in fact short, as expected in the absence of Pauli suppression of collisions. Moreover, measurements of collisions of Li2 with free Li atoms demonstrates a striking first example of collisions involving molecules at ultracold temperatures described by physics beyond universal long-range van der Waals interactions.

  19. Polypetide signaling molecules in plant development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intercellular communication mediated by small signaling molecules is a key mechanism for coordinating plant growth and development. In the past few years, polypeptide signals have been shown to play prominent roles in processes as diverse as shoot and root meristem maintenance, vascular differentiat...

  20. Comprehensive Map of Molecules Implicated in Obesity.

    PubMed

    Jagannadham, Jaisri; Jaiswal, Hitesh Kumar; Agrawal, Stuti; Rawal, Kamal

    2016-01-01

    Obesity is a global epidemic affecting over 1.5 billion people and is one of the risk factors for several diseases such as type 2 diabetes mellitus and hypertension. We have constructed a comprehensive map of the molecules reported to be implicated in obesity. A deep curation strategy was complemented by a novel semi-automated text mining system in order to screen 1,000 full-length research articles and over 90,000 abstracts that are relevant to obesity. We obtain a scale free network of 804 nodes and 971 edges, composed of 510 proteins, 115 genes, 62 complexes, 23 RNA molecules, 83 simple molecules, 3 phenotype and 3 drugs in "bow-tie" architecture. We classify this network into 5 modules and identify new links between the recently discovered fat mass and obesity associated FTO gene with well studied examples such as insulin and leptin. We further built an automated docking pipeline to dock orlistat as well as other drugs against the 24,000 proteins in the human structural proteome to explain the therapeutics and side effects at a network level. Based upon our experiments, we propose that therapeutic effect comes through the binding of one drug with several molecules in target network, and the binding propensity is both statistically significant and different in comparison with any other part of human structural proteome. PMID:26886906

  1. Comprehensive Map of Molecules Implicated in Obesity

    PubMed Central

    Agrawal, Stuti

    2016-01-01

    Obesity is a global epidemic affecting over 1.5 billion people and is one of the risk factors for several diseases such as type 2 diabetes mellitus and hypertension. We have constructed a comprehensive map of the molecules reported to be implicated in obesity. A deep curation strategy was complemented by a novel semi-automated text mining system in order to screen 1,000 full-length research articles and over 90,000 abstracts that are relevant to obesity. We obtain a scale free network of 804 nodes and 971 edges, composed of 510 proteins, 115 genes, 62 complexes, 23 RNA molecules, 83 simple molecules, 3 phenotype and 3 drugs in “bow-tie” architecture. We classify this network into 5 modules and identify new links between the recently discovered fat mass and obesity associated FTO gene with well studied examples such as insulin and leptin. We further built an automated docking pipeline to dock orlistat as well as other drugs against the 24,000 proteins in the human structural proteome to explain the therapeutics and side effects at a network level. Based upon our experiments, we propose that therapeutic effect comes through the binding of one drug with several molecules in target network, and the binding propensity is both statistically significant and different in comparison with any other part of human structural proteome. PMID:26886906

  2. Stability of Matter-Antimatter Molecules

    SciTech Connect

    Wong, Cheuk-Yin; Lee, Teck-Ghee

    2011-01-01

    We examine the stability of matter-antimatter molecules by reducing the four-body problem into a simpler two-body problem with residual interactions. We find that matter-antimatter molecules with constituents (m{sub 1}{sup +}, m{sub 2}{sup -}, {bar m}{sub 2}{sup +}, {bar m}{sub 1}{sup -}) possess bound states if their constituent mass ratio m{sub 1}/m{sub 2} is greater than about 4. This stability condition suggests that the binding of matter-antimatter molecules is a rather common phenomenon. We evaluate the binding energies and eigenstates of matter-antimatter molecules ({mu}{sup +}e{sup 0})-(e{sup +}{mu}{sup -}), ({pi}{sup +}e{sup -})-(e{sup +}{pi}{sup -}), (K{sup +}e{sup -})-(e{sup +}K{sup -}), (pe{sup -})-(e{sup +}{bar p}), (p{mu}{sup -})-({mu}{sup +}{bar p}), and (K{sup +}{mu}{sup -})-({mu}{sup +}K{sup -}), which satisfy the stability condition. We estimate the molecular annihilation lifetimes in their s states.

  3. Molecule diagram from earth-grown crystals

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Like many chemicals in the body, the three-dimensional structure of insulin is extremely complex. When grown on the ground, insulin crystals do not grow as large or as ordered as researchers desire--obscuring the blueprint of the insulin molecules.

  4. Small molecule control of bacterial biofilms

    PubMed Central

    Worthington, Roberta J.; Richards, Justin J.

    2012-01-01

    Bacterial biofilms are defined as a surface attached community of bacteria embedded in a matrix of extracellular polymeric substances that they have produced. When in the biofilm state, bacteria are more resistant to antibiotics and the host immune response than are their planktonic counterparts. Biofilms are increasingly recognized as being significant in human disease, accounting for 80% of bacterial infections in the body and diseases associated with bacterial biofilms include: lung infections of cystic fibrosis, colitis, urethritis, conjunctivitis, otitis, endocarditis and periodontitis. Additionally, biofilm infections of indwelling medical devices are of particular concern, as once the device is colonized infection is virtually impossible to eradicate. Given the prominence of biofilms in infectious diseases, there has been an increased effort toward the development of small molecules that will modulate bacterial biofilm development and maintenance. In this review, we highlight the development of small molecules that inhibit and/or disperse bacterial biofilms through non-microbicidal mechanisms. The review discuses the numerous approaches that have been applied to the discovery of lead small molecules that mediate biofilm development. These approaches are grouped into: 1) the identification and development of small molecules that target one of the bacterial signaling pathways involved in biofilm regulation, 2) chemical library screening for compounds with anti-biofilm activity, and 3) the identification of natural products that possess anti-biofilm activity, and the chemical manipulation of these natural products to obtain analogues with increased activity. PMID:22733439

  5. Organic molecules in translucent interstellar clouds.

    PubMed

    Krełowski, Jacek

    2014-09-01

    Absorption spectra of translucent interstellar clouds contain many known molecular bands of CN, CH+, CH, OH, OH(+), NH, C2 and C3. Moreover, one can observe more than 400 unidentified absorption features, known as diffuse interstellar bands (DIBs), commonly believed to be carried by complex, carbon-bearing molecules. DIBs have been observed in extragalactic sources as well. High S/N spectra allow to determine precisely the corresponding column densities of the identified molecules, rotational temperatures which differ significantly from object to object in cases of centrosymmetric molecular species, and even the (12)C/(13)C abundance ratio. Despite many laboratory based studies of possible DIB carriers, it has not been possible to unambiguously link these bands to specific species. An identification of DIBs would substantially contribute to our understanding of chemical processes in the diffuse interstellar medium. The presence of substructures inside DIB profiles supports the idea that DIBs are very likely features of gas phase molecules. So far only three out of more than 400 DIBs have been linked to specific molecules but none of these links was confirmed beyond doubt. A DIB identification clearly requires a close cooperation between observers and experimentalists. The review presents the state-of-the-art of the investigations of the chemistry of interstellar translucent clouds i.e. how far our observations are sufficient to allow some hints concerning the chemistry of, the most common in the Galaxy, translucent interstellar clouds, likely situated quite far from the sources of radiation (stars). PMID:25467771

  6. Electron-atom /molecule/ collision processes

    NASA Technical Reports Server (NTRS)

    Trajmar, S.

    1980-01-01

    Electron-atom (molecule) collision processes at low and intermediate energies, from near threshold to a few hundred electron volts, are discussed. Attention is given to experimental techniques and procedures, electron impact cross sections, impact excitation and electron-atom scattering in laser fields. Specific examples are presented that illustrate various experimental techniques and interpretations of observations.

  7. Making Excited Oxygen Molecules And Atoms

    NASA Technical Reports Server (NTRS)

    Vasquez, Richard P.

    1989-01-01

    Oxidation of semiconductors and high-temperature superconductors achieved at lower temperatures by use of oxygen molecules or atoms raised into specific excited states. Use of excited oxygen (or other species) of interest in research on kinetics and mechanisms of chemical reactions. Used in ultra-high-vacuum chamber also equipped for such surface-analytical techniques as x-ray photoelectron spectroscopy.

  8. Ion-Molecule Chemistry in Titan's Ionosphere

    NASA Technical Reports Server (NTRS)

    Anicich, V. G.; McEwan, M. J.

    1996-01-01

    We present a summary of the information available from laboratory studies of ion-molecule reactions that is relevant to the chemistry occuring in Titan's ionopshere. Reaction information from the literature has been collated and we have measured many new reations, including some ion-atom reactions.

  9. Progress in Computational Electron-Molecule Collisions

    NASA Astrophysics Data System (ADS)

    Rescigno, Tn

    1997-10-01

    The past few years have witnessed tremendous progress in the development of sophisticated ab initio methods for treating collisions of slow electrons with isolated small molecules. Researchers in this area have benefited greatly from advances in computer technology; indeed, the advent of parallel computers has made it possible to carry out calculations at a level of sophistication inconceivable a decade ago. But bigger and faster computers are only part of the picture. Even with today's computers, the practical need to study electron collisions with the kinds of complex molecules and fragments encountered in real-world plasma processing environments is taxing present methods beyond their current capabilities. Since extrapolation of existing methods to handle increasingly larger targets will ultimately fail as it would require computational resources beyond any imagined, continued progress must also be linked to new theoretical developments. Some of the techniques recently introduced to address these problems will be discussed and illustrated with examples of electron-molecule collision calculations we have carried out on some fairly complex target gases encountered in processing plasmas. Electron-molecule scattering continues to pose many formidable theoretical and computational challenges. I will touch on some of the outstanding open questions.

  10. Proteins Are the Body's Worker Molecules

    MedlinePlus

    ... Each "bead" is a small molecule called an amino acid. There are 20 standard amino acids, each with its own shape, size, and properties. Proteins typically contain from 50 to 2,000 amino acids hooked end-to-end in many combinations. Each ...

  11. Complex organic molecules and star formation

    NASA Astrophysics Data System (ADS)

    Bacmann, A.; Faure, A.

    2014-12-01

    Star forming regions are characterised by the presence of a wealth of chemical species. For the past two to three decades, ever more complex organic species have been detected in the hot cores of protostars. The evolution of these molecules in the course of the star forming process is still uncertain, but it is likely that they are partially incorporated into protoplanetary disks and then into planetesimals and the small bodies of planetary systems. The complex organic molecules seen in star forming regions are particularly interesting since they probably make up building blocks for prebiotic chemistry. Recently we showed that these species were also present in the cold gas in prestellar cores, which represent the very first stages of star formation. These detections question the models which were until now accepted to account for the presence of complex organic molecules in star forming regions. In this article, we shortly review our current understanding of complex organic molecule formation in the early stages of star formation, in hot and cold cores alike and present new results on the formation of their likely precursor radicals.

  12. Molecules of significance in planetary aeronomy

    NASA Technical Reports Server (NTRS)

    Mohan, H.

    1979-01-01

    This monograph is basically devoted to spectroscopic information of the molecules of planetary interest. Only those molecules have been dealt with which have been confirmed spectroscopically to be present in the atmosphere of major planets of our solar system and play an important role in the aeronomy of the respective planets. An introduction giving the general conditions of planets and their atmospheres including the gaseous molecules is given. Some typical planetary spectra is presented and supported with a discussion on some basic concepts of optical absorption and molecular parameters that are important to the study of planetary atmospheres. Quantities like dipole moments, transition probabilities, Einstein coefficients and line strengths, radiative life times, absorption cross sections, oscillator strengths, line widths and profiles, equivalent widths, growth curves, bond strengths, electronic transition moments, Franck-Condon factors and r-centroids, etc., are discussed. Spectroscopic information and relevant data of 6 diatomic (HF, HCL, CO, H2, O2, N2) and 6 polyatomic (CO2, N2), O3, HeO, NH3, CH4) molecules are presented.

  13. Predicting the Stability of Hypervalent Molecules

    ERIC Educational Resources Information Center

    Mitchell, Tracy A.; Finnocchio, Debbie; Kua, Jeremy

    2007-01-01

    An exercise is described which introduces students to using concepts in thermochemistry to predict relative stability of a hypervalent molecule. Students will compare the energies of formation for both fluoride and the hydride by calculations and they will also explore the issue of partial ionic character in polar covalent bonds.

  14. Selective functionalization: Shields for small molecules

    NASA Astrophysics Data System (ADS)

    Silverman, Scott K.

    2012-10-01

    Nucleic acid aptamers have been employed to shield small molecules so that one among many similar reactive functional groups can be modified. This provides access to new chemical entities with potentially interesting properties while avoiding the use of covalent protecting groups.

  15. Uranium-mediated activation of small molecules.

    PubMed

    Arnold, Polly L

    2011-08-28

    Molecular complexes of uranium are capable of activating a range of industrially and economically important small molecules such as CO, CO(2), and N(2); new and often unexpected reactions provide insight into an element that needs to be well-understood if future clean-energy solutions are to involve nuclear power. PMID:21614341

  16. The Molecules of the Cell Membrane.

    ERIC Educational Resources Information Center

    Bretscher, Mark S.

    1985-01-01

    Cell membrane molecules form a simple, two-dimensional liquid controlling what enters and leaves the cell. Discusses cell membrane molecular architecture, plasma membranes, epithelial cells, cycles of endocytosis and exocytosis, and other topics. Indicates that some cells internalize, then recycle, membrane area equivalent to their entire surface…

  17. SMPDB: The Small Molecule Pathway Database.

    PubMed

    Frolkis, Alex; Knox, Craig; Lim, Emilia; Jewison, Timothy; Law, Vivian; Hau, David D; Liu, Phillip; Gautam, Bijaya; Ly, Son; Guo, An Chi; Xia, Jianguo; Liang, Yongjie; Shrivastava, Savita; Wishart, David S

    2010-01-01

    The Small Molecule Pathway Database (SMPDB) is an interactive, visual database containing more than 350 small-molecule pathways found in humans. More than 2/3 of these pathways (>280) are not found in any other pathway database. SMPDB is designed specifically to support pathway elucidation and pathway discovery in clinical metabolomics, transcriptomics, proteomics and systems biology. SMPDB provides exquisitely detailed, hyperlinked diagrams of human metabolic pathways, metabolic disease pathways, metabolite signaling pathways and drug-action pathways. All SMPDB pathways include information on the relevant organs, organelles, subcellular compartments, protein cofactors, protein locations, metabolite locations, chemical structures and protein quaternary structures. Each small molecule is hyperlinked to detailed descriptions contained in the Human Metabolome Database (HMDB) or DrugBank and each protein or enzyme complex is hyperlinked to UniProt. All SMPDB pathways are accompanied with detailed descriptions, providing an overview of the pathway, condition or processes depicted in each diagram. The database is easily browsed and supports full text searching. Users may query SMPDB with lists of metabolite names, drug names, genes/protein names, SwissProt IDs, GenBank IDs, Affymetrix IDs or Agilent microarray IDs. These queries will produce lists of matching pathways and highlight the matching molecules on each of the pathway diagrams. Gene, metabolite and protein concentration data can also be visualized through SMPDB's mapping interface. All of SMPDB's images, image maps, descriptions and tables are downloadable. SMPDB is available at: http://www.smpdb.ca. PMID:19948758

  18. Single molecule dynamics in lipid membranes

    NASA Astrophysics Data System (ADS)

    Skaug, Michael James

    Lipid membranes are self-assembled molecular materials that form the membranes of cells. Because of their biological function, lipid membranes are important from a biomedical and biotechnological standpoint. Because of their complex fluid properties, they also provide a rich testbed for studying the structure and dynamics in self-assembled materials and for developing other bio-mimetic structures. In this work, we studied the dynamics of single lipid molecules using experimental and computational techniques. Using single molecule fluorescence microscopy, we tracked the diffusive motion of lipids in phase separated lipid membranes. With the additional techniques of atomic force microscopy and Monte Carlo simulation, we were able to, for the first time experimentally, directly correlate the observed obstructed diffusion with lipid membrane organization. The single molecule tracking tracking experiments required the addition of impurity fluorescent molecules and the assumption that the impurities do not alter the dynamics of the system. To test this assumption, we performed atomistic molecular dynamics simulations of a fluorescently labeled lipid in a lipid membrane. We showed that the fluorescent impurity could have a significant impact on some membrane properties, such as phase behavior, but that relative changes in diffusive behavior are unaffected.

  19. Photochromism of diarylethene molecules and crystals.

    PubMed

    Irie, Masahiro

    2010-01-01

    Photochromism is defined as a reversible transformation of a chemical species between two isomers upon photoirradiation. Although vast numbers of photochromic molecules have been so far reported, photochromic molecules which exhibit thermally irreversible photochromic reactivity are limited to a few examples. The thermal irreversibility is an indispensable property for the application of photochromic molecules to optical memories and switches. We have developed a new class of photochromic molecules named "diarylethenes", which show the thermally irreversible photochromic reactivity. The well designed diarylethene derivatives provide outstanding photochromic performance: both isomers are thermally stable for more than 470,000 years, photoinduced coloration/decoloration can be repeated more than 10(5) cycles, the quantum yield of cyclization reaction is close to 1 (100%), and the response times of both coloration and decoloration are less than 10 ps. This review describes theoretical background of the photochromic reactions, color changes of the derivatives in solution as well as in the single crystalline phase, and application of the crystals to light-driven actuators. PMID:20467213

  20. Self and directed assembly: people and molecules.

    PubMed

    James, Tony D

    2016-01-01

    Self-assembly and directed-assembly are two very important aspects of supramolecular chemistry. As a young postgraduate student working in Canada with Tom Fyles my introduction to Supramolecular Chemistry was through the self-assembly of phospholipid membranes to form vesicles for which we were developing unimolecular and self-assembling transporter molecules. The next stage of my development as a scientist was in Japan with Seiji Shinkai where in a "Eureka" moment, the boronic acid templating unit (directed-assembly) of Wulff was combined with photoinduced electron transfer systems pioneered by De Silva. The result was a turn-on fluorescence sensor for saccharides; this simple result has continued to fuel my research to the present day. Throughout my career as well as assembling molecules, I have enjoyed bringing together researchers in order to develop collaborative networks. This is where molecules meet people resulting in assemblies worth more than the individual "molecule" or "researcher". My role in developing networks with Japan was rewarded by the award of a Daiwa-Adrian Prize in 2013 and I was recently rewarded for developing networks with China with an Inaugural CASE Prize in 2015. PMID:27340435

  1. Molecules into Cells: Specifying Spatial Architecture

    PubMed Central

    Harold, Franklin M.

    2005-01-01

    A living cell is not an aggregate of molecules but an organized pattern, structured in space and in time. This article addresses some conceptual issues in the genesis of spatial architecture, including how molecules find their proper location in cell space, the origins of supramolecular order, the role of the genes, cell morphology, the continuity of cells, and the inheritance of order. The discussion is framed around a hierarchy of physiological processes that bridge the gap between nanometer-sized molecules and cells three to six orders of magnitude larger. Stepping stones include molecular self-organization, directional physiology, spatial markers, gradients, fields, and physical forces. The knowledge at hand leads to an unconventional interpretation of biological order. I have come to think of cells as self-organized systems composed of genetically specified elements plus heritable structures. The smallest self that can be fairly said to organize itself is the whole cell. If structure, form, and function are ever to be computed from data at a lower level, the starting point will be not the genome, but a spatially organized system of molecules. This conclusion invites us to reconsider our understanding of what genes do, what organisms are, and how living systems could have arisen on the early Earth. PMID:16339735

  2. Electrostatic Propulsion Using C60 Molecules

    NASA Technical Reports Server (NTRS)

    Leifer, Stephanie D.; Saunders, Winston A.

    1993-01-01

    Report proposes use of C60 as propellant material in electrostatic propulsion system of spacecraft. C60, C70, and similar molecules, have recently been found to have characteristics proving advantageous in electrostatic propulsion. Report discusses these characteristics and proposes experiments to determine feasibility of concept.

  3. Calculations of nuclear electric shielding in molecules

    NASA Astrophysics Data System (ADS)

    Lazzeretti, P.; Zanasi, R.

    1980-05-01

    The electric shielding tensor at nuclei in the molecules H 2O, NH 3, CH 4 and CO has been evaluated via coupled Hartree-Fock perturbation theory. The average trace of the shielding tensor is linearly dependent on atomic electronegativities in the isoelectronic series H 2O, NH 3, CH 4.

  4. Copper Keplerates: High-Symmetry Magnetic Molecules.

    PubMed

    Palacios, Maria A; Moreno Pineda, Eufemio; Sanz, Sergio; Inglis, Ross; Pitak, Mateusz B; Coles, Simon J; Evangelisti, Marco; Nojiri, Hiroyuki; Heesing, Christian; Brechin, Euan K; Schnack, Jürgen; Winpenny, Richard E P

    2016-01-01

    Keplerates are molecules that contain metal polyhedra that describe both Platonic and Archimedean solids; new copper keplerates are reported, with physical studies indicating that even where very high molecular symmetry is found, the low-temperature physics does not necessarily reflect this symmetry. PMID:26530901

  5. Organic chemistry: Precision pruning of molecules

    NASA Astrophysics Data System (ADS)

    Yang, Kin S.; Engle, Keary M.

    2016-05-01

    If organic molecules were trees, then the numerous carbon-hydrogen bonds within them would be leaves. A catalyst that targets one 'leaf' out of many similar other ones looks set to be a huge leap for synthetic chemistry. See Letter p.230

  6. Transport properties of asymmetric-top molecules.

    PubMed

    Dickinson, A S; Hellmann, R; Bich, E; Vogel, E

    2007-06-14

    Kinetic theory of gases is extended from linear molecules to asymmetric tops. The integration over the velocity of the centre of mass is carried out explicitly and the results are expressed in a form suitable for classical evaluation. These results can also be employed for spherical and symmetric tops. PMID:17538728

  7. Dynamics of reactive ultracold alkali polar molecules

    NASA Astrophysics Data System (ADS)

    Quéméner, Goulven; Bohn, John; Petrov, Alexander; Kotochigova, Svetlana

    2011-05-01

    Recently, ultracold polar molecules of KRb have been created. These molecules are chemically reactive and their lifetime in a trap is limited. However, their lifetime increases when they are loaded into a 1D optical lattice in the presence of an electric field. These results naturally raise the question of manipulating ultracold collisions of other species of alkali dimer molecules, with an eye toward both novel stereochemistry, as well as suppressing unwanted reactions, to enable condensed matter applications. In this talk, we report on a comparative study between the bi-alkali polar molecules of LiNa, LiK, LiRb, LiCs which have been predicted to be reactive. We compute the isotropic C6 coefficients of these systems and we predict the elastic and reactive rate coefficients when an electric field is applied in a 1D optical lattice. We will discuss the efficacy of evaporative cooling for each species. This work was supported by a MURI-AFOSR grant.

  8. Lesser-Known Molecules in Ovarian Carcinogenesis

    PubMed Central

    Lozneanu, Ludmila; Cojocaru, Elena; Giuşcă, Simona Eliza; Cărăuleanu, Alexandru; Căruntu, Irina-Draga

    2015-01-01

    Currently, the deciphering of the signaling pathways brings about new advances in the understanding of the pathogenic mechanism of ovarian carcinogenesis, which is based on the interaction of several molecules with different biochemical structure that, consequently, intervene in cell metabolism, through their role as regulators in proliferation, differentiation, and cell death. Given that the ensemble of biomarkers in OC includes more than 50 molecules the interest of the researchers focuses on the possible validation of each one's potential as prognosis markers and/or therapeutic targets. Within this framework, this review presents three protein molecules: ALCAM, c-FLIP, and caveolin, motivated by the perspectives provided through the current limited knowledge on their role in ovarian carcinogenesis and on their potential as prognosis factors. Their structural stability, once altered, triggers the initiation of the sequences characteristic for ovarian carcinogenesis, through their role as modulators for several signaling pathways, contributing to the disruption of cellular junctions, disturbance of pro-/antiapoptotic equilibrium, and alteration of transmission of the signals specific for the molecular pathways. For each molecule, the text is built as follows: (i) general remarks, (ii) structural details, and (iii) particularities in expression, from different tumors to landmarks in ovarian carcinoma. PMID:26339605

  9. Microarray analysis at single molecule resolution

    PubMed Central

    Mureşan, Leila; Jacak, Jarosław; Klement, Erich Peter; Hesse, Jan; Schütz, Gerhard J.

    2010-01-01

    Bioanalytical chip-based assays have been enormously improved in sensitivity in the recent years; detection of trace amounts of substances down to the level of individual fluorescent molecules has become state of the art technology. The impact of such detection methods, however, has yet not fully been exploited, mainly due to a lack in appropriate mathematical tools for robust data analysis. One particular example relates to the analysis of microarray data. While classical microarray analysis works at resolutions of two to 20 micrometers and quantifies the abundance of target molecules by determining average pixel intensities, a novel high resolution approach [1] directly visualizes individual bound molecules as diffraction limited peaks. The now possible quantification via counting is less susceptible to labeling artifacts and background noise. We have developed an approach for the analysis of high-resolution microarray images. It consists first of a single molecule detection step, based on undecimated wavelet transforms, and second, of a spot identification step via spatial statistics approach (corresponding to the segmentation step in the classical microarray analysis). The detection method was tested on simulated images with a concentration range of 0.001 to 0.5 molecules per square micron and signal-to-noise ratio (SNR) between 0.9 and 31.6. For SNR above 15 the false negatives relative error was below 15%. Separation of foreground/background proved reliable, in case foreground density exceeds background by a factor of 2. The method has also been applied to real data from high-resolution microarray measurements. PMID:20123580

  10. Method for sequencing nucleic acid molecules

    DOEpatents

    Korlach, Jonas; Webb, Watt W.; Levene, Michael; Turner, Stephen; Craighead, Harold G.; Foquet, Mathieu

    2006-05-30

    The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.

  11. Method for sequencing nucleic acid molecules

    DOEpatents

    Korlach, Jonas; Webb, Watt W.; Levene, Michael; Turner, Stephen; Craighead, Harold G.; Foquet, Mathieu

    2006-06-06

    The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.

  12. Molecules for Fluorescence Detection of Specific Chemicals

    NASA Technical Reports Server (NTRS)

    Fedor, Steve

    2008-01-01

    A family of fluorescent dye molecules has been developed for use in on-off fluorescence detection of specific chemicals. By themselves, these molecules do not fluoresce. However, when exposed to certain chemical analytes in liquid or vapor forms, they do fluoresce (see figure). These compounds are amenable to fixation on or in a variety of substrates for use in fluorescence-based detection devices: they can be chemically modified to anchor them to porous or non-porous solid supports or can be incorporated into polymer films. Potential applications for these compounds include detection of chemical warfare agents, sensing of acidity or alkalinity, and fluorescent tagging of proteins in pharmaceutical research and development. These molecules could also be exploited for use as two-photon materials for photodynamic therapy in the treatment of certain cancers and other diseases. A molecule in this family consists of a fluorescent core (such as an anthracene or pyrene) attached to two end groups that, when the dye is excited by absorption of light, transfer an electron to the core, thereby quenching the fluorescence. The end groups can be engineered so that they react chemically with certain analytes. Upon reaction, electrons on the end groups are no longer available for transfer to the core and, consequently, the fluorescence from the core is no longer quenched. The chemoselectivity of these molecules can be changed by changing the end groups. For example, aniline end groups afford a capability for sensing acids or acid halides (including those contained in chemical warfare agents). Pyridine or bipyridyl end groups would enable sensing of metal ions. Other chemicals that can be selectively detected through suitable choice of end groups include glucose and proteins. Moreover, the fluorescent cores can be changed to alter light-absorption and -emission characteristics: anthracene cores fluoresce at wavelengths around 500 nm, whereas perylene cores absorb and emit at

  13. Chiral Sensitivity in Electron-Molecule Interactions

    NASA Astrophysics Data System (ADS)

    Dreiling, Joan

    2015-09-01

    All molecular forms of life possess a chiral asymmetry, with amino acids and sugars found respectively in L- and D-enantiomers only. The primordial origin of this enantiomeric excess is unknown. One possible explanation is given by the Vester- Ulbricht hypothesis, which suggests that left-handed electrons present in beta-radiation, produced by parity-violating weak decays, interacted with biological precursors and preferentially destroyed one of the two enantiomers. Experimental tests of this idea have thus far yielded inconclusive results. We show direct evidence for chirally-dependent bond breaking through a dissociative electron attachment (DEA) reaction when spin-polarized electrons are incident on gas-phase chiral molecules. This provides unambiguous evidence for a well-defined, chirally-sensitive destructive molecular process and, as such, circumstantial evidence for the Vester-Ulbricht hypothesis. I will also present the results of our systematic study of the DEA asymmetry for different chiral halocamphor molecules. Three halocamphor molecules were investigated: 3-bromocamphor (C10H15BrO), 3-iodocamphor(C10H15IO), and 10-iodocamphor. The DEA asymmetries collected for bromocamphor and iodocamphor are qualitatively different, suggesting that the atomic number of the heaviest atom in the molecule plays a crucial role in the asymmetric interactions. The DEA asymmetry data for 3- and 10-iodocamphor have the same qualitative behavior, but the 10-iodocamphor asymmetry is about twice as large at the lowest energies investigated, so the location of the heavy atom in the camphor molecule also affects the asymmetries. This work was performed at the University of Nebraska-Lincoln. This project is funded by NSF Grant PHY-1206067.

  14. A Supramolecular Approach to Medicinal Chemistry: Medicine Beyond the Molecule

    NASA Astrophysics Data System (ADS)

    Smith, David K.

    2005-03-01

    This article focuses on the essential roles played by intermolecular forces in mediating the interactions between chemical molecules and biological systems. Intermolecular forces constitute a key topic in chemistry programs, yet can sometimes seem disconnected from real-life applications. However, by taking a "supramolecular" view of medicinal chemistry and focusing on interactions between molecules, it is possible to come to a deeper understanding of recent developments in medicine. This allows us to gain a real insight into the interface between biology and chemistry—an interdisciplinary area that is crucial for the development of modern medicinal products. This article emphasizes a conceptual view of medicinal chemistry, which has important implications for the future, as the supramolecular approach to medicinal-chemistry products outlined here is rapidly allowing nanotechnology to converge with medicine. In particular, this article discusses recent developments including the rational design of drugs such as Relenza and Tamiflu, the mode of action of vancomycin, and the mechanism by which bacteria develop resistance, drug delivery using cyclodextrins, and the importance of supramolecular chemistry in understanding protein aggregation diseases such as Alzheimer's and Creutzfield Jacob. The article also indicates how taking a supramolecular approach will enable the development of new nanoscale medicines.

  15. Living is information processing: from molecules to global systems.

    PubMed

    Farnsworth, Keith D; Nelson, John; Gershenson, Carlos

    2013-06-01

    We extend the concept that life is an informational phenomenon, at every level of organisation, from molecules to the global ecological system. According to this thesis: (a) living is information processing, in which memory is maintained by both molecular states and ecological states as well as the more obvious nucleic acid coding; (b) this information processing has one overall function-to perpetuate itself; and (c) the processing method is filtration (cognition) of, and synthesis of, information at lower levels to appear at higher levels in complex systems (emergence). We show how information patterns, are united by the creation of mutual context, generating persistent consequences, to result in 'functional information'. This constructive process forms arbitrarily large complexes of information, the combined effects of which include the functions of life. Molecules and simple organisms have already been measured in terms of functional information content; we show how quantification may be extended to each level of organisation up to the ecological. In terms of a computer analogy, life is both the data and the program and its biochemical structure is the way the information is embodied. This idea supports the seamless integration of life at all scales with the physical universe. The innovation reported here is essentially to integrate these ideas, basing information on the 'general definition' of information, rather than simply the statistics of information, thereby explaining how functional information operates throughout life. PMID:23456459

  16. Fungal quorum sensing molecules: Role in fungal morphogenesis and pathogenicity.

    PubMed

    Wongsuk, Thanwa; Pumeesat, Potjaman; Luplertlop, Natthanej

    2016-05-01

    When microorganisms live together in high numbers, they need to communicate with each other. To achieve cell-cell communication, microorganisms secrete molecules called quorum-sensing molecules (QSMs) that control their biological activities and behaviors. Fungi secrete QSMs such as farnesol, tyrosol, phenylethanol, and tryptophol. The role of QSMs in fungi has been widely studied in both yeasts and filamentous fungi, for example in Candida albicans, C. dubliniensis, Aspergillus niger, A. nidulans, and Fusarium graminearum. QSMs impact fungal morphogenesis (yeast-to-hypha formation) and also play a role in the germination of macroconidia. QSMs cause fungal cells to initiate programmed cell death, or apoptosis, and play a role in fungal pathogenicity. Several types of QSMs are produced during stages of biofilm development to control cell population or morphology in biofilm communities. This review article emphasizes the role of fungal QSMs, especially in fungal morphogenesis, biofilm formation, and pathogenicity. Information about QSMs may lead to improved measures for controlling fungal infection. PMID:26972663

  17. ChemBank: a small-molecule screening and cheminformatics resource database

    PubMed Central

    Seiler, Kathleen Petri; George, Gregory A.; Happ, Mary Pat; Bodycombe, Nicole E.; Carrinski, Hyman A.; Norton, Stephanie; Brudz, Steve; Sullivan, John P.; Muhlich, Jeremy; Serrano, Martin; Ferraiolo, Paul; Tolliday, Nicola J.; Schreiber, Stuart L.; Clemons, Paul A.

    2008-01-01

    ChemBank (http://chembank.broad.harvard.edu/) is a public, web-based informatics environment developed through a collaboration between the Chemical Biology Program and Platform at the Broad Institute of Harvard and MIT. This knowledge environment includes freely available data derived from small molecules and small-molecule screens and resources for studying these data. ChemBank is unique among small-molecule databases in its dedication to the storage of raw screening data, its rigorous definition of screening experiments in terms of statistical hypothesis testing, and its metadata-based organization of screening experiments into projects involving collections of related assays. ChemBank stores an increasingly varied set of measurements derived from cells and other biological assay systems treated with small molecules. Analysis tools are available and are continuously being developed that allow the relationships between small molecules, cell measurements, and cell states to be studied. Currently, ChemBank stores information on hundreds of thousands of small molecules and hundreds of biomedically relevant assays that have been performed at the Broad Institute by collaborators from the worldwide research community. The goal of ChemBank is to provide life scientists unfettered access to biomedically relevant data and tools heretofore available primarily in the private sector. PMID:17947324

  18. Novel Applications of Buffer-gas Cooling to Cold Atoms, Diatomic Molecules, and Large Molecules

    NASA Astrophysics Data System (ADS)

    Drayna, Garrett Korda

    Cold gases of atoms and molecules provide a system for the exploration of a diverse set of physical phenomena. For example, cold gasses of magnetically and electrically polar atoms and molecules are ideal systems for quantum simulation and quantum computation experiments, and cold gasses of large polar molecules allow for novel spectroscopic techniques. Buffer-gas cooling is a robust and widely applicable method for cooling atoms and molecules to temperatures of approximately 1 Kelvin. In this thesis, I present novel applications of buffer-gas cooling to obtaining gases of trapped, ultracold atoms and diatomic molecules, as well as the study of the cooling of large organic molecules. In the first experiment of this thesis, a buffer-gas beam source of atoms is used to directly load a magneto-optical trap. Due to the versatility of the buffer-gas beam source, we obtain trapped, sub-milliKelvin gases of four different lanthanide species using the same experimental apparatus. In the second experiment of this thesis, a buffer-gas beam is used as the initial stage of an experiment to directly laser cool and magneto-optically trap the diatomic molecule CaF. In the third experiment of this thesis, buffer-gas cooling is used to study the cooling of the conformational state of large organic molecules. We directly observe conformational relaxation of gas-phase 1,2-propanediol due to cold collisions with helium gas. Lastly, I present preliminary results on a variety of novel applications of buffer-gas cooling, such as mixture analysis, separation of chiral mixtures, the measurement of parity-violation in chiral molecules, and the cooling and spectroscopy of highly unstable reaction intermediates.

  19. Spin transport in molecules studied by Fe3O4/molecule nanoparticles

    NASA Astrophysics Data System (ADS)

    Yue, F. J.; Wang, S.; Wu, D.

    2013-05-01

    In this work, we synthesize single molecular layer coated Fe3O4 nanoparticles to form the network of the molecular junction spin valves. The Fe3O4 nanoparticles chemically bond with molecules without any physically absorbed molecules, leading to one monolayer molecule coated on nanoparticles. The magnetoresistance (MR) of cold-pressed Fe3O4/oleic acid nanoparticles is more than two times larger than bare Fe3O4 nanoparticles, indicating weaker spin scattering in molecules. Furthermore, the MR ratio is as high as ˜21 % at room temperature for Fe3O4/alkane molecule nanoparticles. Interestingly, even though the resistance spans about two decades as the alkane molecular length varies from 0.7 to 2.5 nm, the MR ratio stays approximately constant. This molecular length independent spin valve MR, originated from the weaker hyperfine interaction strength of the σ-electrons in alkane molecules, entails room-temperature spin-conserving transport in molecular materials. Using the size of ˜500 nm Fe3O4 nanoparticles, a large MR is achieved in a relatively low magnetic field. This feature opens a door for the development of future spin-based molecular electronics. Moreover, spin injection at the interface of Fe3O4/stearic acid molecule is investigated in a comparative study between Fe3O4 nanoparticles chemically bonded (ChemNPs) and physically absorbed (PhyNPs) molecules. A MR of 12 % at room temperature is observed in ChemNPs, in sharp contrast to the zero MR ratio in PhyNPs, reflecting that the chemical bonding is crucial for spin injection. These results show that the hybrid nanoparticles provide a simple approach to study the spin transport in molecules.

  20. NASA's Exobiology Program

    NASA Technical Reports Server (NTRS)

    Devincenzi, D. L.

    1984-01-01

    The goal of NASA's Exobiology Program is to understand the origin, evolution, and distribution of life, and life-related molecules, on earth and throughout the universe. Emphasis is focused on determining how the rate and direction of these processes were affected by the chemical and physical environment of the evolving planet, as well as by planetary, solar, and astrophysical phenomena. This is accomplished by a multi-disciplinary program of research conducted by over 60 principal investigators in both NASA and university laboratories. Major program thrusts are in the following research areas: biogenic elements; chemical evolution; origin of life; organic geochemistry; evolution of higher life forms; solar system exploration; and the search for extraterrestrial intelligence (SETI).

  1. SLIMP: Strong laser interaction model package for atoms and molecules

    NASA Astrophysics Data System (ADS)

    Zhang, Bin; Zhao, Zengxiu

    2015-07-01

    We present the SLIMP package, which provides an efficient way for the calculation of strong-field ionization rate and high-order harmonic spectra based on the single active electron approximation. The initial states are taken as single-particle orbitals directly from output files of the general purpose quantum chemistry programs GAMESS, Firefly and Gaussian. For ionization, the molecular Ammosov-Delone-Krainov theory, and both the length gauge and velocity gauge Keldysh-Faisal-Reiss theories are implemented, while the Lewenstein model is used for harmonic spectra. Furthermore, it is also efficient for the evaluation of orbital coordinates wavefunction, momentum wavefunction, orbital dipole moment and calculation of orbital integrations. This package can be applied to quite large basis sets and complex molecules with many atoms, and is implemented to allow easy extensions for additional capabilities.

  2. Ultrasensitive nucleic acid sequence detection by single-molecule electrophoresis

    SciTech Connect

    Castro, A; Shera, E.B.

    1996-09-01

    This is the final report of a one-year laboratory-directed research and development project at Los Alamos National Laboratory. There has been considerable interest in the development of very sensitive clinical diagnostic techniques over the last few years. Many pathogenic agents are often present in extremely small concentrations in clinical samples, especially at the initial stages of infection, making their detection very difficult. This project sought to develop a new technique for the detection and accurate quantification of specific bacterial and viral nucleic acid sequences in clinical samples. The scheme involved the use of novel hybridization probes for the detection of nucleic acids combined with our recently developed technique of single-molecule electrophoresis. This project is directly relevant to the DOE`s Defense Programs strategic directions in the area of biological warfare counter-proliferation.

  3. Influence of the presence of small gas molecules in the structure of comblike polyacrylates: a Monte Carlo study.

    PubMed

    León, Salvador; Zanuy, David; Alemán, Carlos

    2002-05-01

    A theoretical strategy has been developed to study the motion of small molecules through ordered polymeric systems. The strategy, which has been incorporated into a computer program denoted MCDP/2, is especially useful to study comblike polymers organized in biphasic arrangements. This is because it is based on a configurational bias Monte Carlo algorithm, which is more efficient than conventional methods to study dense systems. The MCDP/2 program has been used to investigate the influence of CH(4) and CO(2) gas molecules in the structure of isotactic poly(octadecyl acrylate), a typical comblike polymer. For this purpose, the pure polymer and different molecular systems constituted by several gas molecules dissolved in the polymer matrix have been simulated. Results indicated that the structural relaxation of the polymer is not coupled to the motion of gas molecules. The importance of these results in the field of molecular modeling of transport properties in comblike polymers is discussed. PMID:11948586

  4. Rotational partition functions for symmetric-top molecules

    NASA Astrophysics Data System (ADS)

    McDowell, Robin S.

    1990-08-01

    An improved expression is found for the rotational partition functions of symmetric-top molecules. The expression includes the effect of nuclear spin for molecules of C(3v) symmetry. The effect that centrifugal distortion of the rotating molecules has on these rigid-rotator formulations is considered. The nuclear-spin correction is generalized to symmetric-top molecules of other symmetries. The treatment is extended to nonplanar molecules that exhibit inversion doubling, with particular attention given to NH3.

  5. Postsecondary Programs.

    ERIC Educational Resources Information Center

    American Annals of the Deaf, 2002

    2002-01-01

    This article lists postsecondary programs specifically for people with deafness and other postsecondary programs with supportive services for students with deafness. Alphabetized by state, contact information is provided for each of the programs, along with date the program was founded, programs, degrees, and number of students and staff with…

  6. Reactive collisions of ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Makrides, Constantinos; Kotochigova, Svetlana; Petrov, Alexander

    2013-05-01

    There has been a recent increase in the number of experimental and theoretical efforts in describing and controlling ultra cold chemistry. A number of groups have been able to create and trap a number of cold molecules and are now looking to move into controlling more exotic molecular systems. Critical to this movement is understanding the various interactions between the atoms and molecules in the trap. We offer here a study of the these interactions using Li + LiYb as a test system of interest. Using ab initio calculations we are able to obtain the long range interactions for the current system and connect to the short range interactions to provide a description of the interaction landscape. With this information, chemical reactions such as the exchange reaction (Li + LiYb --> Yb + Li2) can be practically approached in scattering calculations. We acknowledge funding from the ARO MURI on quantum control of chemical reactions and the National Science Foundation.

  7. Automated imaging system for single molecules

    DOEpatents

    Schwartz, David Charles; Runnheim, Rodney; Forrest, Daniel

    2012-09-18

    There is provided a high throughput automated single molecule image collection and processing system that requires minimal initial user input. The unique features embodied in the present disclosure allow automated collection and initial processing of optical images of single molecules and their assemblies. Correct focus may be automatically maintained while images are collected. Uneven illumination in fluorescence microscopy is accounted for, and an overall robust imaging operation is provided yielding individual images prepared for further processing in external systems. Embodiments described herein are useful in studies of any macromolecules such as DNA, RNA, peptides and proteins. The automated image collection and processing system and method of same may be implemented and deployed over a computer network, and may be ergonomically optimized to facilitate user interaction.

  8. Theory of single molecule emission spectroscopy

    NASA Astrophysics Data System (ADS)

    Bel, Golan; Brown, Frank L. H.

    2015-05-01

    A general theory and calculation framework for the prediction of frequency-resolved single molecule photon counting statistics is presented. Expressions for the generating function of photon counts are derived, both for the case of naive "detection" based solely on photon emission from the molecule and also for experimentally realizable detection of emitted photons, and are used to explicitly calculate low-order photon-counting moments. The two cases of naive detection versus physical detection are compared to one another and it is demonstrated that the physical detection scheme resolves certain inconsistencies predicted via the naive detection approach. Applications to two different models for molecular dynamics are considered: a simple two-level system and a two-level absorber subject to spectral diffusion.

  9. Transport of fullerene molecules along graphene nanoribbons

    PubMed Central

    Savin, Alexander V.; Kivshar, Yuri S.

    2012-01-01

    We study the motion of C60 fullerene molecules and short-length carbon nanotubes on graphene nanoribbons. We reveal that the character of the motion of C60 depends on temperature: for T < 150 K the main type of motion is sliding along the surface, but for higher temperatures the sliding is replaced by rocking and rolling. Modeling of the buckyball with an included metal ion demonstrates that this molecular complex undergoes a rolling motion along the nanoribbon with the constant velocity under the action of a constant electric field. The similar effect is observed in the presence of the heat gradient applied to the nanoribbon, but mobility of carbon structures in this case depends largely on their size and symmetry, such that larger and more asymmetric structures demonstrate much lower mobility. Our results suggest that both electorphoresis and thermophoresis can be employed to control the motion of carbon molecules and fullerenes. PMID:23259049

  10. Artifacts in single-molecule localization microscopy.

    PubMed

    Burgert, Anne; Letschert, Sebastian; Doose, Sören; Sauer, Markus

    2015-08-01

    Single-molecule localization microscopy provides subdiffraction resolution images with virtually molecular resolution. Through the availability of commercial instruments and open-source reconstruction software, achieving super resolution is now public domain. However, despite its conceptual simplicity, localization microscopy remains prone to user errors. Using direct stochastic optical reconstruction microscopy, we investigate the impact of irradiation intensity, label density and photoswitching behavior on the distribution of membrane proteins in reconstructed super-resolution images. We demonstrate that high emitter densities in combination with inappropriate photoswitching rates give rise to the appearance of artificial membrane clusters. Especially, two-dimensional imaging of intrinsically three-dimensional membrane structures like microvilli, filopodia, overlapping membranes and vesicles with high local emitter densities is prone to generate artifacts. To judge the quality and reliability of super-resolution images, the single-molecule movies recorded to reconstruct the images have to be carefully investigated especially when investigating membrane organization and cluster analysis. PMID:26138928

  11. Computational mass spectrometry for small molecules

    PubMed Central

    2013-01-01

    The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline. PMID:23453222

  12. Photochemical dynamics of surface oriented molecules

    SciTech Connect

    Ho, W.

    1992-01-01

    The period 8/01/91-7/31/92 is the first year of a new project titled Photochemical Dynamics of Surface Oriented Molecules'', initiated with DOE Support. The main objective of this project is to understand the dynamics of elementary chemical reactions by studying photochemical dynamics of surface-oriented molecules. In addition, the mechanisms of photon-surface interactions need to be elucidated. The strategy is to carry out experiments to measure the translational energy distribution, as a function of the angle from the surface normal, of the photoproducts by time-of-flight (TOF) technique by varying the photon wavelength, intensity, polarization, and pulse duration. By choosing adsorbates with different bonding configuration, the effects of adsorbate orientation on surface photochemical dynamics can be studied.

  13. The X(3872) boson: Molecule or charmonium

    SciTech Connect

    Suzuki, Mahiko

    2005-08-01

    It has been argued that the mystery boson X(3872) is a molecular state consisting of primarily D{sup 0}{bar D}*{sup 0} + {bar D}{sup 0}D*{sup 0}. In contrast, apparent puzzles and potential difficulties have been pointed out for the charmonium assignment of X(3872). They examine several aspects of these alternatives by semi-quantitative methods since quantitatively accurate results are often hard to reach on them. they point out that some of the observed properties of X(3872), in particular, the binding and the production rates are incompatible with the molecule interpretation. Despite puzzles and obstacles, X(3872) may fit more likely to the excited {sup 3}P{sub 1} charmonium than to the molecule after the mixing of c{bar c} with D{bar D}* + {bar D}D* is taken into account.

  14. Computer display and manipulation of biological molecules

    NASA Technical Reports Server (NTRS)

    Coeckelenbergh, Y.; Macelroy, R. D.; Hart, J.; Rein, R.

    1978-01-01

    This paper describes a computer model that was designed to investigate the conformation of molecules, macromolecules and subsequent complexes. Utilizing an advanced 3-D dynamic computer display system, the model is sufficiently versatile to accommodate a large variety of molecular input and to generate data for multiple purposes such as visual representation of conformational changes, and calculation of conformation and interaction energy. Molecules can be built on the basis of several levels of information. These include the specification of atomic coordinates and connectivities and the grouping of building blocks and duplicated substructures using symmetry rules found in crystals and polymers such as proteins and nucleic acids. Called AIMS (Ames Interactive Molecular modeling System), the model is now being used to study pre-biotic molecular evolution toward life.

  15. Multichannel quantum defect theory for polar molecules

    NASA Astrophysics Data System (ADS)

    Elfimov, Sergei V.; Dorofeev, Dmitrii L.; Zon, Boris A.

    2014-02-01

    Our work is devoted to developing a general approach for nonpenetrating Rydberg states of polar molecules. We propose a method to estimate the accuracy of calculation of their wave functions and quantum defects. Basing on this method we estimate the accuracy of Born-Oppenheimer (BO) and inverse Born-Oppenheimer (IBO) approximations for these states. This estimation enables us to determine the space and energy regions where BO and IBO approximations are valid. It depends on the interplay between l coupling (due to dipole potential of the core) and l uncoupling (due to rotation the core). Next we consider the intermediate region where both BO and IBO are not valid. For this intermediate region we propose a modification of Fano's multichannel quantum defect theory to match BO and IBO wave functions and show that it gives more reliable results. They are demonstrated on the example of SO molecule.

  16. Small molecule inhibition of RISC loading.

    PubMed

    Tan, Grace S; Chiu, Chun-Hao; Garchow, Barry G; Metzler, David; Diamond, Scott L; Kiriakidou, Marianthi

    2012-02-17

    Argonaute proteins are the core components of the microRNP/RISC. The biogenesis and function of microRNAs and endo- and exo- siRNAs are regulated by Ago2, an Argonaute protein with RNA binding and nuclease activities. Currently, there are no in vitro assays suitable for large-scale screening of microRNP/RISC loading modulators. We describe a novel in vitro assay that is based on fluorescence polarization of TAMRA-labeled RNAs loaded to human Ago2. Using this assay, we identified potent small-molecule inhibitors of RISC loading, including aurintricarboxylic acid (IC(50) = 0.47 μM), suramin (IC(50) = 0.69 μM), and oxidopamine HCL (IC(50) = 1.61 μM). Small molecules identified by this biochemical screening assay also inhibited siRNA loading to endogenous Ago2 in cultured cells. PMID:22026461

  17. Theory of single molecule emission spectroscopy

    SciTech Connect

    Bel, Golan; Brown, Frank L. H.

    2015-05-07

    A general theory and calculation framework for the prediction of frequency-resolved single molecule photon counting statistics is presented. Expressions for the generating function of photon counts are derived, both for the case of naive “detection” based solely on photon emission from the molecule and also for experimentally realizable detection of emitted photons, and are used to explicitly calculate low-order photon-counting moments. The two cases of naive detection versus physical detection are compared to one another and it is demonstrated that the physical detection scheme resolves certain inconsistencies predicted via the naive detection approach. Applications to two different models for molecular dynamics are considered: a simple two-level system and a two-level absorber subject to spectral diffusion.

  18. Graphene-porphyrin single-molecule transistors

    NASA Astrophysics Data System (ADS)

    Mol, Jan A.; Lau, Chit Siong; Lewis, Wilfred J. M.; Sadeghi, Hatef; Roche, Cecile; Cnossen, Arjen; Warner, Jamie H.; Lambert, Colin J.; Anderson, Harry L.; Briggs, G. Andrew D.

    2015-07-01

    We demonstrate a robust graphene-molecule-graphene transistor architecture. We observe remarkably reproducible single electron charging, which we attribute to insensitivity of the molecular junction to the atomic configuration of the graphene electrodes. The stability of the graphene electrodes allow for high-bias transport spectroscopy and the observation of multiple redox states at room-temperature.We demonstrate a robust graphene-molecule-graphene transistor architecture. We observe remarkably reproducible single electron charging, which we attribute to insensitivity of the molecular junction to the atomic configuration of the graphene electrodes. The stability of the graphene electrodes allow for high-bias transport spectroscopy and the observation of multiple redox states at room-temperature. Electronic supplementary information (ESI) available. See DOI: 10.1039/C5NR03294F

  19. Interstellar molecules - Formation in solar nebulae

    NASA Technical Reports Server (NTRS)

    Anders, E.

    1973-01-01

    Herbig's (1970) hypothesis that solar nebulae might be the principal source of interstellar grains and molecules is investigated. The investigation includes the determination of physical and chemical conditions in the early solar system. The production of organic compounds in the solar nebula is studied, and the compounds in meteorites are compared with those obtained in Miller-Urey and Fischer-Tropsch-type (FTT) reactions, taking into consideration aliphatic hydrocarbons, aromatic hydrocarbons, purines, pyrimidines, amino acids, porphyrins, and aspects of carbon-isotope fractionation. It is found that FTT reactions account reasonably well for all well-established features of organic matter in meteorites investigated. The distribution of compounds produced by FTT reactions is compared with the distribution of interstellar molecules. Biological implications of the results are considered.

  20. - Fourier Transform Infrared Spectroscopy of Small - Molecules

    NASA Astrophysics Data System (ADS)

    Li, G.; Bernath, P. F.

    2011-06-01

    A series of small boron-containing molecules were synthesized in the gas phase using a tube furnace. High-resolution spectra of these species were recorded in either emission or absorption in the mid-infrared region using a Bruker IFS-125HR spectrometer. Our observations contain vibration-rotation bands of BO, the V1 and V3 bands of HBO, the V1 and V3 bands of HBS, the V1 band of FBO, and the V1 band of HBF2. The vibrational bands of HOBO, BF2OH and other boron-containing molecules may also be present. Ab initio calculations were performed at the MRCI level to assist in the vibrational assignments. Preliminary assignments of the spectra for these species will be reported.