Single-strand breaks （SSBs） can occur in cells either directly, or indirectly following initiation of base excision repair （BER）. SSBs generally have blocked termini lacking the conventional 5＇-phosphate and 3＇-...Single-strand breaks （SSBs） can occur in cells either directly, or indirectly following initiation of base excision repair （BER）. SSBs generally have blocked termini lacking the conventional 5＇-phosphate and 3＇-hydroxyl groups and require further processing prior to DNA synthesis and ligation. XRCC1 is devoid of any known enzymatic activity, but it can physically interact with other proteins involved in all stages of the overlapping SSB repair and BER pathways, including those that conduct the rate-limiting end-tailoring, and in many cases can stimulate their enzymatic activities. XRCC1^-/- mouse fibroblasts are most hypersensitive to agents that produce DNA lesions repaired by monofunctional glycosylase-initiated BER and that result in formation of indirect SSBs. A requirement for the deoxyribose phosphate lyase activity of DNA polymerase β （pol β） is specific to this pathway, whereas pol β is implicated in gap-filling during repair of many types of SSBs. Elevated levels of strand breaks, and diminished repair, have been demonstrated in MMS- treated XRCC1^-/-, and to a lesser extent in pol β^-/- cell lines, compared with wild-type cells. Thus a strong correlation is observed between cellular sensitivity to MMS and the ability of cells to repair MMS-induced damage. Exposure of wild-type and polβ^-/- cells to an inhibitor of PARP activity dramatically potentiates MMS-induced cytotoxicity. XRCC1^-/- cells are also sensitized by PARP inhibition demonstrating that PARP-mediated poly（ADP-ribosyl）ation plays a role in modulation of cytotoxicity beyond recruitment of XRCC 1 to sites of DNA damage.展开更多
AIM： TO analyze the percentages of hepatocytes with increased nuclear DNA content, i.e., tetraploid （4n） and octoploid （Sn） nuclei, and then compared mononuclear and binuclear hepatocyte populations： METHODS： T...AIM： TO analyze the percentages of hepatocytes with increased nuclear DNA content, i.e., tetraploid （4n） and octoploid （Sn） nuclei, and then compared mononuclear and binuclear hepatocyte populations： METHODS： The percentages of mononuclear diploid （2n）, 4n, and 8n hepatocytes and those of binuclear 2 × 2n, 2 × 4n, and 2 × 8n hepatocytes were determined with a method that can simultaneously measure hepatocyte nuclear DNA content and binuclearity in 62 patients with chronic hepatitis B or C. The percentage of 4n and 8n hepatocytes in the mononuclear hepatocyte population was compared with the percentage of 2 × 4n and 2 × 8n hepatocytes in the binuclear hepatocyte population. RESULTS： The percentages of 4n and 8n hepatocytes in mononuclear hepatocytes and 2 ×4n and 2 × 8n hepatocytes in binuclear hepatocytes were similar, regardless of the activity or fibrosis grade of chronic hepatitis and regardless of the infecting virus. CONCLUSION： The distribution of nuclear DNA content within mononuclear and binuclear hepatocyte populations was conserved during the course of chronic viral hepatitis.展开更多
Heap overflow attack is one of the major memory corruption attacks that have become prevalent for decades. To defeat this attack,many protection methods are proposed in recent years. However,most of these existing met...Heap overflow attack is one of the major memory corruption attacks that have become prevalent for decades. To defeat this attack,many protection methods are proposed in recent years. However,most of these existing methods focus on user-level heap overflow detection. Only a few methods are proposed for kernel heap protection. Moreover,all these kernel protection methods need modifying the existing OS kernel so that they may not be adopted in practice. To address this problem,we propose a lightweight virtualization-based solution that can protect the kernel heap buffers allocated for the target kernel modules. The key idea of our approach is to combine the static binary analysis and virtualization technology to trap a memory allocation operation of the target kernel module,and then add one secure canary word to the end of the allocated buffer. After that,a monitor process is launched to check the integrity of the canaries. The evaluations show that our system can detect kernel heap overflow attacks effectively with minimal performance cost.展开更多
文摘Single-strand breaks （SSBs） can occur in cells either directly, or indirectly following initiation of base excision repair （BER）. SSBs generally have blocked termini lacking the conventional 5＇-phosphate and 3＇-hydroxyl groups and require further processing prior to DNA synthesis and ligation. XRCC1 is devoid of any known enzymatic activity, but it can physically interact with other proteins involved in all stages of the overlapping SSB repair and BER pathways, including those that conduct the rate-limiting end-tailoring, and in many cases can stimulate their enzymatic activities. XRCC1^-/- mouse fibroblasts are most hypersensitive to agents that produce DNA lesions repaired by monofunctional glycosylase-initiated BER and that result in formation of indirect SSBs. A requirement for the deoxyribose phosphate lyase activity of DNA polymerase β （pol β） is specific to this pathway, whereas pol β is implicated in gap-filling during repair of many types of SSBs. Elevated levels of strand breaks, and diminished repair, have been demonstrated in MMS- treated XRCC1^-/-, and to a lesser extent in pol β^-/- cell lines, compared with wild-type cells. Thus a strong correlation is observed between cellular sensitivity to MMS and the ability of cells to repair MMS-induced damage. Exposure of wild-type and polβ^-/- cells to an inhibitor of PARP activity dramatically potentiates MMS-induced cytotoxicity. XRCC1^-/- cells are also sensitized by PARP inhibition demonstrating that PARP-mediated poly（ADP-ribosyl）ation plays a role in modulation of cytotoxicity beyond recruitment of XRCC 1 to sites of DNA damage.
文摘AIM： TO analyze the percentages of hepatocytes with increased nuclear DNA content, i.e., tetraploid （4n） and octoploid （Sn） nuclei, and then compared mononuclear and binuclear hepatocyte populations： METHODS： The percentages of mononuclear diploid （2n）, 4n, and 8n hepatocytes and those of binuclear 2 × 2n, 2 × 4n, and 2 × 8n hepatocytes were determined with a method that can simultaneously measure hepatocyte nuclear DNA content and binuclearity in 62 patients with chronic hepatitis B or C. The percentage of 4n and 8n hepatocytes in the mononuclear hepatocyte population was compared with the percentage of 2 × 4n and 2 × 8n hepatocytes in the binuclear hepatocyte population. RESULTS： The percentages of 4n and 8n hepatocytes in mononuclear hepatocytes and 2 ×4n and 2 × 8n hepatocytes in binuclear hepatocytes were similar, regardless of the activity or fibrosis grade of chronic hepatitis and regardless of the infecting virus. CONCLUSION： The distribution of nuclear DNA content within mononuclear and binuclear hepatocyte populations was conserved during the course of chronic viral hepatitis.
基金supported in part by National Natural Science Foundation of China (NSFC) under Grant No.61602035the National Key Research and Development Program of China under Grant No.2016YFB0800700+1 种基金the Opening Project of Shanghai Key Laboratory of Integrated Administration Technologies for Information SecurityOpen Found of Key Laboratory of IOT Application Technology of Universities in Yunnan Province under Grant No.2015IOT03
文摘Heap overflow attack is one of the major memory corruption attacks that have become prevalent for decades. To defeat this attack,many protection methods are proposed in recent years. However,most of these existing methods focus on user-level heap overflow detection. Only a few methods are proposed for kernel heap protection. Moreover,all these kernel protection methods need modifying the existing OS kernel so that they may not be adopted in practice. To address this problem,we propose a lightweight virtualization-based solution that can protect the kernel heap buffers allocated for the target kernel modules. The key idea of our approach is to combine the static binary analysis and virtualization technology to trap a memory allocation operation of the target kernel module,and then add one secure canary word to the end of the allocated buffer. After that,a monitor process is launched to check the integrity of the canaries. The evaluations show that our system can detect kernel heap overflow attacks effectively with minimal performance cost.
