Constraining the Mass of the Photon with Gamma-Ray Bursts

One of the cornerstones of modern physics is Einstein's special relativity, with its constant speed of light and zero photon mass assumptions. Constraint on the rest mass m_{\gamma} of photons is a fundamental way to test Einstein's theory, as well as other essential electromagnetic and particle theories. Since non-zero photon mass can give rise to frequency-(or energy-) dependent dispersions, measuring the time delay of photons with different frequencies emitted from explosive astrophysical events is an important and model-independent method to put such a constraint. The cosmological gamma-ray bursts (GRBs), with short time scales, high redshifts as well as broadband prompt and afterglow emissions, provide an ideal testbed for m_{\gamma} constraints. In this paper we calculate the upper limits of the photon mass with GRB early time radio afterglow observations as well as multi-band radio peaks, thus improve the results of Schaefer (1999) by nearly half an order of magnitude.Comment: 25 pages, 2 tables, Accepted by Journal of High Energy Astrophysic

(3-Pyrid­yl)methanaminium 4-nitro­phenolate 4-nitro­phenol solvate

In the crystal structure of the title compound, C6H9N2 +·C6H4NO3 −·C6H5NO3, ions and mol­ecules are connected via inter­molecular N—H⋯O, N—H⋯N, O—H⋯O and C—H⋯O hydrogen bonds into a three-dimensional network

MECHANISM OF ORLISTAT HYDROLYSIS BY FATTY ACID SYNTHASE THIOESTERASE

poster abstractFatty acid synthase (FASN) is the sole protein capable of de novo synthesis of free fatty acids. The fatty acid synthesis cycle begins with the condensa-tion of acetyl-CoA and malonyl-CoA, and continues with the elongation of the fatty acid chain, which is tethered to an acyl carrier protein domain (ACP), via a repeating cycle. At the end of elongation, the thioesterase (TE) domain of FASN cleaves the bond between the fatty acid and ACP, releasing the fatty acid. FASN has been found to be over-expressed in a wide variety of human cancers, and this over-expression is correlated to a higher meta-static potential and poorer prognosis in cancer patients. Orlistat, an FDA ap-proved drug for obesity treatment, is a compound found to reversibly inhibit FASN TE by covalently binding to the active site serine within the TE domain. In crystal structure studies, a hydrolyzed form of orlistat can also be ob-served in the active site of TE, demonstrating that orlistat is not a stable in-hibitor of FASN. In this study, we examined the mechanism of orlistat hy-drolysis within the TE domain of FASN using molecular dynamics simula-tions. We found that the hexanoyl tail of orlistat is capable of shifting while covalently bound to the active site serine, and that this shift is accompanied by the destabilization of a hydrogen bond that exists between a hydroxyl moiety of orlistat and the active site histidine, allowing a catalytic water molecule to enter the active site with the proper orientation for catalysis of the covalent bond between orlistat and serine. These findings suggest that the hexanoyl tail of orlistat plays an important role in its hydrolysis and may guide the future design of new inhibitors that target the TE domain of FASN with greater endurance for potential use in the treatment of cancer

Diethyl 2,2′-[(5-dimethyl­amino-1-naphth­yl)sulfonyl­imino]diacetate

In the title compound, C20H26N2O6S, the N atom of the dimethyl­amino group is displaced by 0.113 (2) Å from the plane of the naphthalene ring system. The two eth­oxy groups adopt zigzag conformations. In the crystal structure, weak inter­molecular C—H⋯O hydrogen bonds link the mol­ecules, forming a three-dimensional network. Both ethyl groups are disordered over two sites with the ratios of refined occupancies being 0.857 (16):0.143 (16) and 0.517 (14):0.483 (14)

Long-term Blood Pressure Prediction with Deep Recurrent Neural Networks

Existing methods for arterial blood pressure (BP) estimation directly map the input physiological signals to output BP values without explicitly modeling the underlying temporal dependencies in BP dynamics. As a result, these models suffer from accuracy decay over a long time and thus require frequent calibration. In this work, we address this issue by formulating BP estimation as a sequence prediction problem in which both the input and target are temporal sequences. We propose a novel deep recurrent neural network (RNN) consisting of multilayered Long Short-Term Memory (LSTM) networks, which are incorporated with (1) a bidirectional structure to access larger-scale context information of input sequence, and (2) residual connections to allow gradients in deep RNN to propagate more effectively. The proposed deep RNN model was tested on a static BP dataset, and it achieved root mean square error (RMSE) of 3.90 and 2.66 mmHg for systolic BP (SBP) and diastolic BP (DBP) prediction respectively, surpassing the accuracy of traditional BP prediction models. On a multi-day BP dataset, the deep RNN achieved RMSE of 3.84, 5.25, 5.80 and 5.81 mmHg for the 1st day, 2nd day, 4th day and 6th month after the 1st day SBP prediction, and 1.80, 4.78, 5.0, 5.21 mmHg for corresponding DBP prediction, respectively, which outperforms all previous models with notable improvement. The experimental results suggest that modeling the temporal dependencies in BP dynamics significantly improves the long-term BP prediction accuracy.Comment: To appear in IEEE BHI 201

Prevalence and determinants of resistant hypertension among hypertensive patients attending a cardiology clinic in China: a prospective cross-sectional study

Purpose: To determine occurrence and determinants of resistant hypertension (RHT) among patients attending cardiology clinic of the affiliated hospital of Hangzhou Normal University, China.Methods: An observational prospective cross-sectional study was conducted among patients with hypertension attending the cardiology clinic over a period of 6 months. After identification of patients with RHT, various independent co-variants were tested by logistic regression in order to evaluate the determinants of RHT.Results: Out of 556 patients, 104 (18.7 %) patients had RHT while 67 (12.1 %) patients had uncontrolled blood pressure (BP) in spite of treatment with three antihypertensive drugs including a diuretic; 37 (6.6 %) patients had controlled BP with > three drugs. Obesity (OR: 2.7, p = 0.002], duration of hypertension (OR: 1.8, p = 0.015], presence of diabetes mellitus (OR: 3.6, p < 0.001) and ischemic heart disease (OR: 3.2, p = 0.001) were significant determinants of resistant hypertension in the study cohort.Conclusion: The prevalence of RHT found in this study is significantly high, thus indicating a need for greater attention of clinicians to this highly morbid condition. Obese patients and those suffering from diabetes mellitus, ischemic heart disease and chronic diseases should be evaluated for the presence of RHT. Early identification of such patients will provide sufficient time for clinicians to refer patients, as well as modify and/or intensify therapy.Keywords: Resistant hypertension, Risk factors, Hypertension, Stroke, Diabetes mellitus, Ischemic heart diseas

Two decades of research in discovery of anticancer drugs targeting STAT3, how close are we?

Signal transducer and activator of transcription 3 (STAT3) controls many biological processes including differentiation, survival, proliferation, and angiogenesis. In normal healthy cells, STAT3 is tightly regulated to maintain a momentary active state. However, aberrant or constitutively activated STAT3 has been observed in many different cancers and constitutively activated STAT3 has been shown to associate with poor prognosis and tumor progression. For this reason, STAT3 has been studied as a possible target in the treatment of many different types of cancers. However, despite decades of research, a FDA-approved STAT3 inhibitor has yet to emerge. In this review, we will analyze past studies targeting STAT3 for drug discovery, understand possible causes of failure in these studies, and provide potential insights for future efforts to overcome these roadblocks