Efficient Serverless Function Scheduling at the Network Edge

Serverless computing is a promising approach for edge computing since its inherent features, e.g., lightweight virtualization, rapid scalability, and economic efficiency. However, previous studies have not studied well the issues of significant cold start latency and highly dynamic workloads in serverless function scheduling, which are exacerbated at the resource-limited network edge. In this paper, we formulate the Serverless Function Scheduling (SFS) problem for resource-limited edge computing, aiming to minimize the average response time. To efficiently solve this intractable scheduling problem, we first consider a simplified offline form of the problem and design a polynomial-time optimal scheduling algorithm based on each function's weight. Furthermore, we propose an Enhanced Shortest Function First (ESFF) algorithm, in which the function weight represents the scheduling urgency. To avoid frequent cold starts, ESFF selectively decides the initialization of new function instances when receiving requests. To deal with dynamic workloads, ESFF judiciously replaces serverless functions based on the function weight at the completion time of requests. Extensive simulations based on real-world serverless request traces are conducted, and the results show that ESFF consistently and substantially outperforms existing baselines under different settings

MutS Homologues hMSH4 and hMSH5: Genetic Variations, Functions, and Implications in Human Diseases

The prominence of the human mismatch repair (MMR) pathway is clearly reflected by the causal link between MMR gene mutations and the occurrence of Lynch syndrome (or HNPCC). The MMR family of proteins also carries out a plethora of diverse cellular functions beyond its primary role in MMR and homologous recombination. In fact, members of the MMR family of proteins are being increasingly recognized as critical mediators between DNA damage repair and cell survival. Thus, a better functional understanding of MMR proteins will undoubtedly aid the development of strategies to effectively enhance apoptotic signaling in response to DNA damage induced by anti-cancer therapeutics. Among the five known human MutS homologs, hMSH4 and hMSH5 form a unique heterocomplex. However, the expression profiles of the two genes are not correlated in a number of cell types, suggesting that they may function independently as well. Consistent with this, these two proteins are promiscuous and thought to play distinct roles through interacting with different binding partners. Here, we describe the gene and protein structures of eukaryotic MSH4 and MSH5 with a particular emphasis on their human homologues, and we discuss recent findings of the roles of these two genes in DNA damage response and repair. Finally, we delineate the potential links of single nucleotide polymorphism (SNP) loci of these two genes with several human diseases

MutS Homologues hMSH4 and hMSH5: Genetic Variations, Functions, and Implications in Human Diseases

The prominence of the human mismatch repair (MMR) pathway is clearly reflected by the causal link between MMR gene mutations and the occurrence of Lynch syndrome (or HNPCC). The MMR family of proteins also carries out a plethora of diverse cellular functions beyond its primary role in MMR and homologous recombination. In fact, members of the MMR family of proteins are being increasingly recognized as critical mediators between DNA damage repair and cell survival. Thus, a better functional understanding of MMR proteins will undoubtedly aid the development of strategies to effectively enhance apoptotic signaling in response to DNA damage induced by anti-cancer therapeutics. Among the five known human MutS homologs, hMSH4 and hMSH5 form a unique heterocomplex. However, the expression profiles of the two genes are not correlated in a number of cell types, suggesting that they may function independently as well. Consistent with this, these two proteins are promiscuous and thought to play distinct roles through interacting with different binding partners. Here, we describe the gene and protein structures of eukaryotic MSH4 and MSH5 with a particular emphasis on their human homologues, and we discuss recent findings of the roles of these two genes in DNA damage response and repair. Finally, we delineate the potential links of single nucleotide polymorphism (SNP) loci of these two genes with several human diseases

MutS homologue hMSH5: role in cisplatin-induced DNA damage response

BACKGROUND: Cisplatin (cis-diamminedichloroplatinum (II), CDDP) and its analogues constitute an important class of anticancer drugs in the treatment of various malignancies; however, its effectiveness is frequently affected by mutations in genes involved in the repair and signaling of cisplatin-induced DNA damage. These observations necessitate a need for a better understanding of the molecular events governing cellular sensitivity to cisplatin. RESULTS: Here, we show that hMSH5 mediates sensitization to cisplatin-induced DNA damage in human cells. Our study indicates that hMSH5 undergoes cisplatin-elicited protein induction and tyrosine phosphorylation. Silencing of hMSH5 by RNAi or expression of hMSH5 phosphorylation-resistant mutant hMSH5(Y742F )elevates cisplatin-induced G2 arrest and renders cells susceptible to cisplatin toxicity at clinically relevant doses. In addition, our data show that cisplatin promotes hMSH5 chromatin association and hMSH5 deficiency increases cisplatin-triggered γ-H2AX foci. Consistent with a possible role for hMSH5 in recombinational repair of cisplatin-triggered double-strand breaks (DSBs), the formation of cisplatin-induced hMSH5 nuclear foci is hRad51-dependent. CONCLUSION: Collectively, our current study has suggested a role for hMSH5 in the processing of cisplatin-induced DSBs, and silencing of hMSH5 may provide a new means to improve the therapeutic efficacy of cisplatin

Hot deformation behavior and flow stress modeling of annealed AZ61 Mg alloys

In this study, the hyperbolic-sine type constitutive equation was used to model the flow stress of annealed AZ61 magnesium (Mg) alloys. Hot compression tests were conducted at the temperatures ranging from 250 °C to 450 °C and at the strain rates ranging from 1×10–3 s−1 to 1 s−1 on a Gleeble-3500 thermo-simulation machine. Constitutive equations as a function of strain were established through a simple extension of the hyperbolic sine constitutive relation. The effects of annealing heat treatments on the variations in constitutive parameters with strain were discussed. The hot compressive flow curves exhibited typical features of dynamic recrystallization. Multiple peak flow curves were observed in the annealed specimens upon testing at a strain rate of 1×10−1 s–1 and at various temperatures. Variations in constitutive parameters with strain were related to flow behavior and dependent on the initial conditions of the test specimens. The flow stresses of annealed AZ61 Mg alloys were predicted well by the strain-dependent constitutive equations of the hyperbolic sine function under the deformation conditions employed in this study

The causal link between microsatellite instability and hMRE11 dysfunction in human cancers

Maintenance of genomic integrity is essential for cell survival, and genomic instability is a commonly recognized intrinsic property of all cancers. Microsatellite instability (MSI) represents a frequently occurring and easily traceable simple form of sequence variation signified by the contraction or expansion of specific DNA sequences containing short tandem repeats. MSI is frequently detected in tumor cells with DNA mismatch repair (MMR) deficiency. It is commonly conceived that instability at individual microsatellite loci can arise spontaneously in cells independent of MMR status, and different microsatellite loci are generally not affected uniformly by MMR deficiency. It is well recognized that MMR deficiency per se is not sufficient to initiate tumorigenesis; rather the biological effects have to be exerted by mutations in genes controlling cell survival, DNA damage response, and apoptosis. Recently, shortening of an intronic hMRE11 poly(T)11 tract has been associated with MMR deficiency, raising the possibility that hMRE11 may be inactivated by defective MMR. However, the molecular nature underlying this association is presently unknown, and review of the current literature suggests that hMRE11 is most likely involved with the MMR pathway in a more complex fashion than just being a MMR target gene. An alternative scenario is proposed to better reconcile the differences among various studies. The potential role of hMRE11 in telomere repeats stability is also discussed

Analogy circuit synthesis and dynamics confirmation of a bipolar pulse current-forced 2D Wilson neuron model

Neurons can exhibit abundant electrical activities in response to various externally applied stimuli, which can lay the groundwork for widening their use in neuron-based engineering applications. This paper presents the dynamical behaviors and analogy circuit-based confirmations in a bipolar pulse (BP) current-forced two-dimensional (2D) Wilson neuron model. Due to the existence of BP current, the proposed 2D neuron model has periodically switchable equilibrium states. The BP current-associated dynamical behaviors, including subthreshold oscillation (STO), periodic limit cycle, chaos, and antimonotonicity phenomenon, are numerically revealed by common dynamical analyses. Note that the electrical activity behaves a close dependence on the frequency of the externally applied BP current. Thereafter, an analog circuit is optimally synthesized to implement the 2D Wilson neuron model by utilizing the off-the-shelf discrete components, upon which the Multisim 12.0-based circuit simulations and hardware experiments are executed. It is revealed that the circuit-simulated and experimentally captured results well confirm the numerically simulated ones