Au nanostructured surfaces for electrochemical and localized surface plasmon resonance-based monitoring of α-synuclein-small molecule interactions.

In this proof-of-concept study, the fabrication of novel Au nanostructured indium tin oxide (Au-ITO) surfaces is described for the development of a dual-detection platform with electrochemical and localized surface plasmon resonance (LSPR)-based biosensing capabilities. Nanosphere lithography (NSL) was applied to fabricate Au-ITO surfaces. Oligomers of α-synuclein (αS) were covalently immobilized to determine the electrochemical and LSPR characteristics of the protein. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were performed using the redox probe [Fe(CN)6](3-/4-) to detect the binding of Cu(II) ions and (-)-epigallocatechin-3-gallate (EGCG) to αS on the Au-ITO surface. Electrochemical and LSPR data were complemented by Thioflavin-T (ThT) fluorescence, surface plasmon resonance imaging (SPRi), and transmission electron microscopy (TEM) studies. EGCG was shown to induce the formation of amorphous aggregates that decreased the electrochemical signals. However, the binding of EGCG with αS increased the LSPR absorption band with a bathochromic shift of 10-15 nm. The binding of Cu(II) to αS enhanced the DPV peak current intensity. NSL fabricated Au-ITO surfaces provide a promising dual-detection platform to monitor the interaction of small molecules with proteins using electrochemistry and LSPR

A Phase II Study of Concurrent Docetaxel, Epirubicin and Cyclophosphamide as a Neoadjuvant Chemotherapy Regimen in Patients with Locally Advanced Breast Cancer

Background: Neoadjuvant chemotherapy with concurrent docetaxel, doxorubicin and cyclophosphamide is commonly used for patients with locally advanced breast cancer. Epirubicin is another anthracycline used in breast cancer but the concurrent use of epirubicin and taxane is not well-established. We conducted a single institution, phase II study to assess the efficacy and safety of concurrent docetaxel, epirubicin and cyclophosphamide (TEC) as a neoadjuvant chemotherapy regimen in breast cancer. Methods: Patients with newly diagnosed locally advanced breast cancer defined as T2 >3 cm, T3, T4 with any N, or any T with N1-3 were eligible. A chemotherapy regimen of docetaxel 75mg/m2, epirubicin 75mg/m2 and cyclophosphamide 600mg/m2 was given with filgrastim support every 3 weeks for 6 cycles. The primary end-point was pathologic complete response rate. Results: Twenty patients were enrolled from 2003 to 2006. The median age was 51 (29-70) year-old. Eight patients were premenopausal. Ten patients had positive hormone receptors. Four patients had HER2 positive receptor. Nineteen patients completed six cycles of TEC chemotherapy. The pathologic complete response rate was 25%. Eight of sixteen patients with N1-3 disease had pathological negative lymph nodes. With a median follow up of 57.5 (16-71) months, four patients relapsed including one death from recurrence. The estimated 5 year relapse-free survival was 79.3% and the 5-year overall survival was 94.7%. No patient had cardiac failure or death during treatment. The most common grade 3-4 toxicity was neutropenia (35%). Conclusion: TEC regimen is a well- tolerated and effective neoadjuvant chemotherapy regimen for locally advanced breast cancer that results in a pathologic complete response rate of 25%

What Makes Good In-context Demonstrations for Code Intelligence Tasks with LLMs?

Pre-trained models of source code have gained widespread popularity in many code intelligence tasks. Recently, with the scaling of the model and corpus size, large language models have shown the ability of in-context learning (ICL). ICL employs task instructions and a few examples as demonstrations, and then inputs the demonstrations to the language models for making predictions. This new learning paradigm is training-free and has shown impressive performance in various natural language processing and code intelligence tasks. However, the performance of ICL heavily relies on the quality of demonstrations, e.g., the selected examples. It is important to systematically investigate how to construct a good demonstration for code-related tasks. In this paper, we empirically explore the impact of three key factors on the performance of ICL in code intelligence tasks: the selection, order, and number of demonstration examples. We conduct extensive experiments on three code intelligence tasks including code summarization, bug fixing, and program synthesis. Our experimental results demonstrate that all the above three factors dramatically impact the performance of ICL in code intelligence tasks. Additionally, we summarize our findings and provide takeaway suggestions on how to construct effective demonstrations, taking into account these three perspectives. We also show that a carefully-designed demonstration based on our findings can lead to substantial improvements over widely-used demonstration construction methods, e.g., improving BLEU-4, EM, and EM by at least 9.90%, 175.96%, and 50.81% on code summarization, bug fixing, and program synthesis, respectivelyComment: This paper is accepted by ASE 202

Otopetrin 1 protects mice from obesity-associated metabolic dysfunction through attenuating adipose tissue inflammation.

Chronic low-grade inflammation is emerging as a pathogenic link between obesity and metabolic disease. Persistent immune activation in white adipose tissue (WAT) impairs insulin sensitivity and systemic metabolism, in part, through the actions of proinflammatory cytokines. Whether obesity engages an adaptive mechanism to counteract chronic inflammation in adipose tissues has not been elucidated. Here we identified otopetrin 1 (Otop1) as a component of a counterinflammatory pathway that is induced in WAT during obesity. Otop1 expression is markedly increased in obese mouse WAT and is stimulated by tumor necrosis factor-α in cultured adipocytes. Otop1 mutant mice respond to high-fat diet with pronounced insulin resistance and hepatic steatosis, accompanied by augmented adipose tissue inflammation. Otop1 attenuates interferon-γ (IFN-γ) signaling in adipocytes through selective downregulation of the transcription factor STAT1. Using a tagged vector, we found that Otop1 physically interacts with endogenous STAT1. Thus, Otop1 defines a unique target of cytokine signaling that attenuates obesity-induced adipose tissue inflammation and plays an adaptive role in maintaining metabolic homeostasis in obesity

White, Man, and Highly Followed: Gender and Race Inequalities in Twitter

Social media is considered a democratic space in which people connect and interact with each other regardless of their gender, race, or any other demographic factor. Despite numerous efforts that explore demographic factors in social media, it is still unclear whether social media perpetuates old inequalities from the offline world. In this paper, we attempt to identify gender and race of Twitter users located in U.S. using advanced image processing algorithms from Face++. Then, we investigate how different demographic groups (i.e. male/female, Asian/Black/White) connect with other. We quantify to what extent one group follow and interact with each other and the extent to which these connections and interactions reflect in inequalities in Twitter. Our analysis shows that users identified as White and male tend to attain higher positions in Twitter, in terms of the number of followers and number of times in user's lists. We hope our effort can stimulate the development of new theories of demographic information in the online space.Comment: In Proceedings of the IEEE/WIC/ACM International Conference on Web Intelligence (WI'17). Leipzig, Germany. August 201

Impaired insulin secretion of aging: Role of renal failure and hyperparathyroidism

Impaired insulin secretion of aging: Role of renal failure and hyperparathyroidism. Available data indicate that insulin secretion is impaired with aging. Almost all the studies that examined insulin secretion by old animals did not take into consideration the state of renal function or the blood levels of parathyroid hormone (PTH). Old animals may have chronic renal failure (CRF) and secondary hyperparathyroidism, and both of these conditions impair insulin secretion. It is possible, therefore, that the impaired insulin secretion of aging is not due to old age per se, but rather to associated CRF and excess PTH. The present study examined this issue in adult (6 month old) and senescent rats (2 years old) with and without CRF and excess PTH. Senescent rats without CRF had normal renal function and normal blood levels of PTH, and the values were not different from those observed in adult rats. Creatinine clearance in senescent rats with CRF was significantly (P < 0.01) lower and serum levels of PTH were significantly (P < 0.01) higher than in senescent animals without CRF and than in the adult rats as well. Only the senescent rats with CRF displayed glucose intolerance during intravenous glucose tolerance test. For any given level of blood glucose, plasma insulin levels were lower in senescent rats with CRF than in the adult rat or senescent animals without CRF. Both initial phase (139 ± 45 pg/islet · 8 min) and total (808 ± 216 pg/islet · 33 min) insulin secretion from pancreatic islets of the senescent rats with CRF and excess PTH were significantly lower than those in senescent rats with normal renal function (658 ± 117 pg/islet · 8 min and 3294 ± 290 pg/islet · 33 min, respectively) or in adult rats (710 ± 134 pg/islet · 8 min and 3183 ± 366 pg/islet · 33 min, respectively). There were no significant differences in insulin secretion between the adult rats and the senescent ones with normal renal function. The data demonstrate that the impaired insulin secretion by the pancreatic islets in old rats is not necessarily related to the higher age per se, but is due to the associated CRF and secondary hyperparathyroidism that develops in many, but not all old animals. Our results indicate that studies examining the effect of aging on body function should take into consideration the level of renal function and of the serum PTH, since both CRF and excess PTH adversely affect the functional integrity of many organs

Two-body Cabibbo-suppressed Decays of Charmed Baryons into Vector Mesons and into Photons

The heavy quark effective theory and the factorization approximation are used to treat the Cabibbo-suppressed decays of charmed baryons to vector mesons, $\Lambda_C\rightarrow p{\rho^0}, p\omega$, $\Xi_C^{+,0}\rightarrow\Sigma^{+,0}\phi, \Sigma^{+,0}{\rho^0}, \Sigma^{+,0}\omega$ and $\Xi_C^{0}\rightarrow\Lambda\phi, \Lambda\rho, \Lambda\omega$. The input from two recent experimental results on $\Lambda_C$ decays allows the estimation of the branching ratios for these modes, which turn out to be between $10^{-4}$ and $10^{-3}$. The long distance contribution of these transitions via vector meson dominance to the radiative weak processes $\Lambda_C\rightarrow p\gamma$, $\Xi_C\rightarrow\Sigma\gamma$ and $\Xi_C^0\rightarrow\Lambda\gamma$ leads to quite small branching ratios, $10^{-6}-10^{-9}$; the larger value holds if a sum rule between the coupling constants of the vector mesons is broken.Comment: 11 pages, latex, no figure

Novel hypoglycemic injury mechanism: N-methyl-D-aspartate receptor-mediated white matter damage

Objective: Hypoglycemia is a common adverse event and can injure central nervous system (CNS) white matter (WM). We determined if glutamate receptors were involved in hypoglycemic WM injury. Methods: Mouse optic nerves (MON), CNS WM tracts, were maintained at 37°C with oxygenated artificial cerebrospinal fluid (ACSF) containing 10 mM glucose. Aglycemia was produced by switching to 0 glucose ACSF. Supra-maximal compound action potentials (CAPs) were elicited using suction electrodes and axon function was quantified as the area under the CAP. Amino acid release was measured using HPLC. Extracellular [lactate] was measured using an enzyme electrode. Results: About 50% of MON axons were injured after 60 min of aglycemia (90% after 90 min); injury was not affected by animal age. Blockade of NMDA-type glutamate receptors improved recovery after 90 min of aglycemia by 250%. Aglycemic injury was increased by reducing [Mg2+]o or increasing [glycine]o, and decreased by lowering pHo, expected results for NMDA receptor-mediated injury. Extracellular pH increased during aglycemia, due to a drop in [lactate-]o. Aglycemic injury was dramatically reduced in the absence of [Ca2+]o. Extracellular aspartate, a selective NMDA receptor agonist, increased during aglycemia. Interpretation: Aglycemia injured WM by a unique excitotoxic mechanism involving NMDA receptors (located primarily on oligodendrocytes). During WM aglycemia, the selective NMDA agonist, aspartate, is released, probably from astrocytes. Injury is mediated by Ca2+ influx through aspartate-activated NMDA receptors made permeable by an accompanying alkaline shift in pHo caused by a fall in [lactate-]o. These insights have important clinical implications