What is life? A perspective of the mathematical kinetic theory of active particles

The modeling of living systems composed of many interacting entities is treated in this paper with the aim of describing their collective behaviors. The mathematical approach is developed within the general framework of the kinetic theory of active particles. The presentation is in three parts. First, we derive the mathematical tools, subsequently, we show how the method can be applied to a number of case studies related to well defined living systems, and finally, we look ahead to research perspectives

The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex.

The amyloid-β peptide or Aβ is the key player in the amyloid-cascade hypothesis of Alzheimer's disease. Aβ appears to trigger cell death but also production of double-strand breaks (DSBs) in aging and Alzheimer's disease. All-trans retinoic acid (RA), a derivative of vitamin A, was already known for its neuroprotective effects against the amyloid cascade. It diminishes, for instance, the production of Aβ peptides and their oligomerisation. In the present work we investigated the possible implication of RA receptor (RAR) in repair of Aβ-induced DSBs. We demonstrated that RA, as well as RAR agonist Am80, but not AGN 193109 antagonist, repair Aβ-induced DSBs in SH-SY5Y cells and an astrocytic cell line as well as in the murine cortical tissue of young and aged mice. The nonhomologous end joining pathway and the Ataxia Telangiectasia Mutated kinase were shown to be involved in RA-mediated DSBs repair in the SH-SY5Y cells. Our data suggest that RA, besides increasing cell viability in the cortex of young and even of aged mice, might also result in targeted DNA repair of genes important for cell or synaptic maintenance. This phenomenon would remain functional up to a point when Aβ increase and RA decrease probably lead to a pathological state

Symmetry of zygomatic bone through 3D segmentation on CT-scan and "mirroring" procedure: a novel approach for reconstructive maxillofacial surgery

Zygomatic bones are among those most frequently fractured facial bones [1]: symmetry is the golden standard for a correct restoration of zygomatic shape, but literature is divided about the best method for its quantification. Also, no information about the actual 3D symmetry of this bone in healthy subjects is available. This study aims at exposing an innovative approach for the assessment of zygomatic symmetry through 3D surface analysis. One hundred patients (50 males and 50 females) were selected from the CT-scans database from a Northern Italy hospital. Zygomatic bones from each patient were segmented, the left bone was automatically mirrored according to the sagittal plane and registered on the right one according to the least point-to-point distance between the two surfaces. Mean and RMS (root mean square) distance between the two models was then calculated. Possible statistically significant differences according to sex and age groups were assessed respectively through two-way ANOVA test (p0.05). This study first provides an overall assessment of symmetry of zygomatic bone, based on surface analysis: results may provide a useful indication for the reconstruction of zygomatic bones in maxillofacial surgery

Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients Under Trastuzumab Therapy for Primary Operable Breast Cancer Overexpressing Her2

Preliminary results from a pilot trial on trastuzumab's mechanism of action against operable breast tumors overexpressing Her2 suggested a role for antibody-dependent cell cytotoxicity (ADCC). To examine factors affecting ADCC intensity and variability, we extended this study to the phenotypic and functional analysis of circulating mononuclear cells in 18 patients. ADCC was induced by trastuzumab therapy in 15 of 18 patients (83%). Inability to develop ADCC in three patients did not depend on inadequate levels of trastuzumab because further increase in its concentration in vitro was ineffective. Rather, susceptibility to develop ADCC was fairly predicted by test with trastuzumab before therapy and was correlated to the number of lymphocytes coexpressing CD16 and CD56. Phenotypic analysis at the end of ADCC evaluating down-regulation of CD16, and up-regulation of CD69 and CD107a, confirmed that natural killer (NK) cells and CD56+ T cells were involved in productive engagement of trastuzumab. Also, the killing efficiency of CD16+ lymphocytes was influenced by 158 V/F polymorphism of FcγRIII (CD16), whereas variations of CD247 on NK cells were consistent with trends between ADCC before and after therapy. Complete pathologic response was observed in one patient showing ADCC of outstanding intensity, whereas four cases of partial response showed intermediate ADCC; none of the three patients unable to mount ADCC had significant tumor regression. These data indicate that quantity and lytic efficiency of CD16+ lymphocytes are major factors for ADCC induction by trastuzumab, and confirm that breast cancer responses to short-term trastuzumab monotherapy may depend on involvement of the ADCC mechanism. [Cancer Res 2007;67(24):11991–9

In vitro hypoxia-conditioned colon cancer cell lines derived from HCT116 and HT29 exhibit altered apoptosis susceptibility and a more angiogenic profile in vivo

Hypoxia is an important selective force in the clonal evolution of tumours. Through HIF-1 and other transcription factors combined with tumour-specific genetic alterations, hypoxia is a dominant factor in the angiogenic phenotype. Cellular adaptation to hypoxia is an important requirement of tumour progression independent of angiogenesis. The adaptive changes, insofar as they alter hypoxia-induced apoptosis, are likely to determine responsiveness to antiangiogenic strategies. To investigate this adaptation of tumour cells to hypoxia, we recreated in vitro the in vivo situation of chronic intermittent exposure to low-oxygen levels. The colon carcinoma cell lines HT29 and HCT116 were subjected to 40 episodes of sublethal hypoxia (4 h) three times a week. The resulting two hypoxia-conditioned cell lines have been maintained in culture for more than 2 years. In both cell lines changes in doubling times occurred: in HT29 an increase, and in HCT116 a decrease. Cell survival in response to hypoxia and to DNA damage differed strikingly in the two cell lines. The HT29 hypoxia-conditioned cells were more resistant than the parental line to a 24 h hypoxic challenge, while those from HCT116 surprisingly were more sensitive. Sensitivity to cisplatin in vitro was also significantly different for the hypoxia-conditioned compared with the parental lines, suggesting a change in pathways leading to apoptosis following DNA damage signaling. The growth of both conditioned cell lines in vivo as xenografts in immunodeficient (SCID) mice was more rapid than their parental lines, and was accompanied in each by evidence of enhanced vascular proliferation as a consequence of the hypoxia-conditioning. Thus the changes in apoptotic susceptibility were independent of altered angiogenesis. The derivation of these lines provides a model for events within hypoxic regions of colon cancers, and for the acquisition of resistance and sensitivity characteristics that may have therapeutic implications for the use of antiangiogenesis drugs

A unified multiscale vision of behavioral crowds

This paper proposes a multiscale vision to human crowds which provides a consistent description at the three possible modeling scales, namely, microscopic, mesoscopic, and macroscopic. The proposed approach moves from interactions at the microscopic scale and shows how the same modeling principles lead to kinetic and hydrodynamic models. Hence, a unified framework is developed which permits to derive models at each scale using the same principles and similar parameters. This approach can be used to simulate crowd dynamics in complex environments composed of interconnected areas, where the most appropriate scale of description can be selected for each area. This offers a pathway to the development of a multiscale computational model which has the capability to optimize the granularity of the description depending on the pedestrian local flow conditions. An important feature of the modeling at each scale is that the complex interaction between emotional states of walkers and their motion is taken into account

Quanti capi ha il muscolo quadricipite? : nuove scoperte

Nello studio dell\u2019anatomia si \ue8 abituati a pensare che l\u2019anatomia sia una scienza \u201cferma\u201d e che le conoscenze del corpo umano si siano esaurite durante gli studi universitari: in realt\ue0 \ue8 una scienza in continua evoluzione, tanto che negli ultimi anni sono stati scoperti elementi di cui prima non si era a conoscenza. Per esempio, sembrerebbe che il muscolo quadricipite non sia effettivamente composto da quattro capi, ma da cinque, o cos\uec almeno in una certa percentuale di soggetti. Una curiosit\ue0 interessante.In the study of anatomy, we have become accustomed to thinking that anatomy is a \u201cnon-evolving\u201d science and that one\u2019s knowledge of the human body is completed and full by the end of one\u2019s university studies. In actual fact, it is a science that is constantly evolving, so much so that in recent years new elements have been uncovered that before were unknown. For example, it would seem that the quadriceps muscle does not actually consist of four heads, but of five, or so at least in a certain proportion of individuals. An interesting curiosity

Interaction of heat with chemotherapy in vitro: effect on cell viability and protein synthesis in human and murine cell lines.

Cell survival in response to doxorubicin (Dx) and cis-diammine-dichloroplatinum (cis-Pt) administration, either alone or combined with hyperthermic treatment, was analyzed in human osteosarcoma (U-2-OS), murine melanoma (B16V) and murine leukemia (P388) cell lines and in Dx-resistant sublines derived from B16V and P388. In all cell lines tested there was an enhancement of drug toxicity by hyperthermia. In U-2-OS, the increase was more pronounced for cis-Pt than for Dx. In B16V and in P388, the increase in Dx toxicity was of the same degree in Dx-sensitive and Dx-resistant sublines, whereas heat-induced sensitization to cis-Pt was higher in Dx-resistant sublines than in their Dx-sensitive counterpart. Analysis of the protein pattern in the various cell lines showed that the synthesis of heat-shock proteins induced by heat was not influenced by the combined use of drugs and heat. Moreover, in spite of some differences in the overall protein pattern, no significant differences in the basal levels of heat-shock protein synthesis or in the extent of its induction after heat shock were observed between murine cell lines relatively sensitive to Dx and their corresponding selected resistant cells