A Practical System for Guaranteed Access in the Presence of DDoS Attacks and Flash Crowds

With the growing incidents of flash crowds and sophisticated DDoS attacks mimicking benign traffic, it becomes challenging to protect Internet-based services solely by differentiating attack traffic from legitimate traffic. While fair-sharing schemes are commonly suggested as a defense when differentiation is difficult, they alone may suffer from highly variable or even unbounded waiting times. We propose RainCheck Filter (RCF), a lightweight primitive that guarantees bounded waiting time for clients despite server flooding without keeping per-client state on the server. RCF achieves strong waiting time guarantees by prioritizing clients based on how long the clients have waited-as if the server maintained a queue in which the clients lined up waiting for service. To avoid keeping state for every incoming client request, the server sends to the client a raincheck, a timestamped cryptographic token that not only informs the client to retry later but also serves as a proof of the client's priority level within the virtual queue. We prove that every client complying with RCF can access the server in bounded time, even under a flash crowd incident or a DDoS attack. Our large-scale simulations confirm that RCF provides a small and predictable maximum waiting time while existing schemes cannot. To demonstrate its deployability, we implement RCF as a Python module such that web developers can protect a critical server resource by adding only three lines of code.Comment: 16 pages, a full technical report for 'A Practical System for Guaranteed Access in the Presence of DDoS Attacks and Flash Crowds' in IEEE International Conference on Network Protocols, 201

Biomechanical microenvironment regulates fusogenicity of breast cancer cells

Fusion of cancer cells is thought to contribute to tumor development and drug resistance. The low frequency of cell fusion events and the instability of fused cells have hindered our ability to understand the molecular mechanisms that govern cell fusion. We have demonstrated that several breast cancer cell lines can fuse into multinucleated giant cells in vitro, and the initiation and longevity of fused cells can be regulated solely by biophysical factors. Dynamically tuning the adhesive area of the patterned substrates, reducing cytoskeletal tensions pharmacologically, altering matrix stiffness, and modulating pattern curvature all supported the spontaneous fusion and stability of these multinucleated giant cells. These observations highlight that the biomechanical microenvironment of cancer cells, including the matrix rigidity and interfacial curvature, can directly modulate their fusogenicity, an unexplored mechanism through which biophysical cues regulate tumor progression

Synthesis and structure-activity relationship studies of novel 3,9-substituted α-carboline derivatives with high cytotoxic activity against colorectal cancer cells

In our continued focus on 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs, we synthesized a novel series of 3,9-substituted α-carboline derivatives and evaluated the new compounds for antiproliferactive effects. Structure activity relationships revealed that a COOCH or CHOH group at position-3 and substituted benzyl group at position-9 of the α-carboline nucleus were crucial for maximal activity. The most active compound, , showed high levels of cytotoxicity against HL-60, COLO 205, Hep 3B, and H460 cells with IC values of 0.3, 0.49, 0.7, and 0.8 μM, respectively. The effect of compound on the cell cycle distribution demonstrated G2/M arrest in COLO 205 cells. Furthermore, mechanistic studies indicated that compound induced apoptosis by activating death receptor and mitochondria dependent apoptotic signaling pathways in COLO 205 cells. The new 3,9-substituted α-carboline derivatives exhibited excellent anti-proliferative activities, and compound can be used as a promising pro-apoptotic agent for future development of new antitumor agents

EXTRACELLULAR MATRIX STIFFNESS AS A CUE TO SHAPE PHENOTYPIC EVOLUTION OF TRIPLE NEGATIVE BREAST CANCER

Accumulation of epigenetic and genetic changes results in oncogenic transformation of epithelial cells. During breast cancer metastasis, while the extracellular matrix (ECM) becomes stiffer, breast cancer cells transmit mechanical forces into intracellular tension and activate signaling pathways influencing growth, migration, and metastasis. Once cancer cells detach from the primary tumor, they intravasate into the vasculature, survive in the circulation, extravasate and adapt to a new microenvironment of a secondary site. Throughout the process, only a very small population of cancer cells survive, and they are likely to reside at the metastatic sites for several years. The most frequent metastatic sites for breast cancer are brain, lung, liver, and bone. Each has distinct mechanical and biochemical properties. To recapitulate this selection process, we grew triple negative breast cancer (TNBC) on soft and stiff biomaterials in addition to the widely used cell culture platform, tissue culture polystyrene over time. Alterations in phenotypes and gene expressions were captured. Since TNBC is heterogeneous, we were interested in investigating the phenotypes of their subclonal compositions. By isolating subclones from the established TNBC cell lines, we were able to measure variations in growth, motility, response to ECM stiffness and proteins, and drug response, etc

Moderate Risk of Hepatitis B Virus Reactivation in HBsAg−/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis

AbstractTo investigate the incidence and risk factors of hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)−/ HBV core antibody (HBcAb)+ patients who underwent rituximab (RTX) therapy for rheumatoid arthritis (RA). From January 2000 through December 2017, a total of 134 RA patients with various HBV serostatuses who received RTX at Dalin Tzu Chi Hospital were screened. Finally, 50 HBsAg−/HBcAb+ patients were enrolled in this retrospective study. Baseline characteristics, comedications, and the occurrence of HBV reactivation were recorded. Four HBsAg−/HBcAb+ RA patients (8%; 4/50) experienced HBV reactivation after treatment with RTX. Hepatitis flare-up occurred in 2 of these 4 patients, with a fatal outcome in one. HBV reactivation occurred approximately 1–4 years after the first dose of RTX and 0.5–1.5 years after the last one. In HBsAg−/HBcAb+ patients, HBV reactivation was significantly more common in those who were HBV surface antibody (HBsAb)− at baseline than in those who were HBsAb+ (30% vs 4%; p = 0.02). A history of adalimumab use was associated with HBV reactivation (100% vs 39%; p = 0.02). A moderate risk of HBV reactivation was observed in HBsAg−/HBcAb+ RA patients receiving RTX therapy. The reactivation may induce acute hepatitis and even death. To reduce the risk of HBV reactivation, regular monitoring of liver function is insufficient; monitoring of viral load and HBsAg or prophylaxis with antiviral therapy should be considered.</jats:p

Fiber Monitoring System Applied to Railway Bridge Structures in a Near-Fault Region

Bridges are widely used for train transportation. Some bridges must be constructed close to geologic faults or across them due to the constraints of travel route alignment and the geographical environment. Taiwan is located at the junction of the Eurasian Plate and the Philippine Plate, where geological joints are present and earthquakes are frequent. In Taiwan, the monitoring and early warning of structural displacements is increasingly important, especially in the mutual control and monitoring of bridges and railways. This study utilizes fiber as a continuous sensor to monitor the safety of railway bridges in a near-fault region. This research builds upon the theory of Brillouin frequency shift (BFS) and applies it to a practical scenario of a fault-crossing railway bridge. BFS is related to the strain and temperature change in a single-mode fiber. Distributed fiber optic sensing (DFOS) systems enable us to detect shifts in frequency on the sensing fiber. A systemic approach to installing DFOS systems will be discussed. Data from a DFOS system are collected, and through data processing, they are converted into strain with regard to the deformations (bending, tension, compression) of a box girder bridge. Changes in the geometric structure of the box girder bridge throughout the year are measured and processed into graphical data. This system can be effectively applied to the structural safety monitoring of railway bridges. Through this research, several functions have been achieved, including continuous displacement, automatic monitoring, and real-time automatic alarm functions, without the need for human intervention

Hepatitis B virus Reactivation in Patients Receiving Tocilizumab for Rheumatoid Arthritis: A Long‐term, Retrospective Observational Study

Abstract Aim To investigate the risk of hepatitis B virus (HBV) reactivation in patients undergoing long-term tocilizumab (TCZ) therapy for rheumatoid arthritis (RA). Method From January 2011 through August 2019, a total of 134 RA patients who received TCZ at Dalin Tzu Chi Hospital were screened. Patients were excluded if they were &lt; 20 years, without complete data, or received TCZ for less than 3 months. A total of 97 patients were enrolled in this retrospective study. Clinical data, co-medications, and the occurrence of HBV reactivation were recorded. Results Of the 97 enrolled patients, 7 were HBsAg+ (7.2%), 64 were HBsAg−/HBcAb+ (61%) and 26 were HBsAg−/HBcAb+ (26.8%). The median disease follow-up time was 9 years (range, 1–18 years). TCZ was administered for a median of 29 months (range, 3–91 months). Four patients (4.1%) experienced HBV reactivation after TCZ therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients had no antiviral prophylaxis, and all 3 (100%) experienced early HBV reactivation and hepatitis flare (median time to event, 6 months; range, 5–8 months). Hyper-bilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg−/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 10 7 IU/mL) after 18 months of TCZ treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare. Conclusions HBsAg+ RA patients undergoing TCZ treatment are at high risk of HBV reactivation, which is prevented by antiviral prophylaxis. HBsAg−/HBcAb+ patients also are at risk of HBV reactivation. Although their risk of reactivation is lower than that of HBsAg+ patients, strict monitoring of their HBV status is still necessary.</jats:p