HOW TO MAKE THE HILL CIPHER SECURE

ABSTRACT

This paper presents a symmetric cipher that is actually a variation of the Hill cipher. The new scheme makes use of “random” permutations of columns and rows of a matrix to form a “different” key for each data encryption. The cipher has matrix products and permutations as the only operations which may be performed “efficiently” by primitive operators, when the system parameters are carefully chosen.     

In vitro assessment of endothelial cell adhesion mechanism on vascular patches

Endothelial cell (EC) seeding of small caliber vascular grafts prior to their implantation has proved to significantly improve long-term patency in humans. We have previously demonstrated that a monolayer of EC could be obtained on type I collagen-coated knitted ultrathin polyster grafts (InterVascular, La Ciotat, France). Thus, the aim of the present work was to understand the nature of cell adhesion mechanisms involved in the cell /biomaterial interface, using HemaCarotid^® (InterVascular) patches made of type I collagen-coated knitted ultrathin polyster (type I collagen is used to coat patches to attain low permeability). By means of quantitative attachment tests, adhesion blocking assays, RT–PCR for the expression of ₁ integrin mRNA, indirect immunofluorescence with antivinculin antibody, we were able to show that EC are able to adhere to such surfaces by the means (non-unique) of cell surface receptors of the ₁ integrin group. However, the latter are probably downregulated at the cell/biomaterial interface.     

Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival

The relationship between Ca2+ release ("Ca2+ sparks") through ryanodine-sensitive Ca2+ release channels in the sarcoplasmic reticulum and KCa channels was examined in smooth muscle cells from rat cerebral arteries. Whole cell potassium currents at physiological membrane potentials (-40 mV) and intracellular Ca2+ were measured simultaneously, using the perforated patch clamp technique and a laser two-dimensional (x-y) scanning confocal microscope and the fluorescent Ca2+ indicator, fluo-3. Virtually all (96%) detectable Ca2+ sparks were associated with the activation of a spontaneous transient outward current (STOC) through KCa channels. A small number of sparks (5 of 128) were associated with currents smaller than 6 pA (mean amplitude, 4.7 pA, at -40 mV). Approximately 41% of STOCs occurred without a detectable Ca2+ spark. The amplitudes of the Ca2+ sparks correlated with the amplitudes of the STOCs (regression coefficient 0.8; P < 0.05). The half time of decay of Ca2+ sparks (56 ms) was longer than the associated STOCs (9 ms). The mean amplitude of the STOCs, which were associated with Ca2+ sparks, was 33 pA at -40 mV. The mean amplitude of the "sparkless" STOCs was smaller, 16 pA. The very significant increase in KCa channel open probability (>10(4)-fold) during a Ca2+ spark is consistent with local Ca2+ during a spark being in the order of 1-100 microM. Therefore, the increase in fractional fluorescence (F/Fo) measured during a Ca2+ spark (mean 2.04 F/Fo or approximately 310 nM Ca2+) appears to significantly underestimate the local Ca2+ that activates KCa channels. These results indicate that the majority of ryanodine receptors that cause Ca2+ sparks are functionally coupled to KCa channels in the surface membrane, providing direct support for the idea that Ca2+ sparks cause STOCs.     

Bcl-xL regulates apoptosis by heterodimerization-dependent and -independent mechanisms

A hydrophobic cleft formed by the BH1, BH2 and BH3 domains of Bcl-xL is responsible for interactions between Bcl-xL and BH3-containing death agonists. Mutants were constructed which did not bind to Bax but retained anti-apoptotic activity. Since Bcl-xL can form an ion channel in synthetic lipid membranes, the possibility that this property has a role in heterodimerization-independent cell survival was tested by replacing amino acids within the predicted channel-forming domain with the corresponding amino acids from Bax. The resulting chimera showed a reduced ability to adopt an open conductance state over a wide range of membrane potentials. Although this construct retained the ability to heterodimerize with Bax and to inhibit apoptosis, when a mutation was introduced that rendered the chimera incapable of heterodimerization, the resulting protein failed to prevent both apoptosis in mammalian cells and Bax-mediated growth defect in yeast. Similar to mammalian cells undergoing apoptosis, yeast cells expressing Bax exhibited changes in mitochondrial properties that were inhibited by Bcl-xL through heterodimerization-dependent and -independent mechanisms. These data suggest that Bcl-xL regulates cell survival by at least two distinct mechanisms; one is associated with heterodimerization and the other with the ability to form a sustained ion channel.     

Changes in mediobasal hypothalamic gonadotropin-releasing hormone messenger ribonucleic acid levels induced by mating or ovariectomy in a reflex ovulator, the ferret

The ferret is a reflex-ovulating species in which receipt of an intromission induces a prolonged (+/- 12 h) preovulatory LH surge in the estrous female. This LH surge is probably stimulated by a large release of GnRH from the mediobasal hypothalamus (MBH). In Exp 1 we asked whether GnRH messenger RNA (mRNA) levels increase in response to mating so as to replenish the MBH GnRH stores needed to sustain the preovulatory LH surge. Estrous females were killed 0, 0.25, 0.5, 1, 3, 6, 14, or 24 h after the onset of a 10-min intromission from a male. Coronal brain sections ranging from the rostral preoptic area caudally to the posterior hypothalamus were processed for in situ hybridization using a 35S-labeled oligoprobe complementary to the human GnRH-coding region. We found no evidence of increased MBH GnRH mRNA levels during the ferret's mating-induced preovulatory LH surge. Instead, the number of GnRH mRNA-expressing cells dropped significantly in the arcuate region beginning 6 h after onset of intromission and remained low thereafter. Furthermore, cellular GnRH mRNA levels decreased in the arcuate region toward the end of the preovulatory LH surge. In Exp 2 we asked whether ovarian hormones regulate MBH GnRH mRNA levels in the female ferret. Ovariectomy of estrous females significantly reduced the number of GnRH mRNA-expressing cells in the arcuate region. This decrease was probably not due to the absence of circulating estradiol. Gonadally intact anestrous females had levels of MBH GnRH mRNA similar to those in estrous females even though plasma estradiol levels were equally low in anestrous females and ovariectomized females. Ovarian hormones other than estradiol may stimulate MBH GnRH mRNA levels in anestrous and estrous females.     

A tuberculin screening and isoniazid preventive therapy program in an inner-city population

As tuberculosis transmission decreases, case rates decline and an increasing proportion of cases arises from the pool of persons with latent infection. Elimination of tuberculosis will require preventing disease from developing in infected persons. From 1994 to 1996 the Atlanta TB Prevention Coalition conducted a community-based tuberculin screening and isoniazid preventive therapy project among high-risk inner-city residents of Atlanta, Georgia. We established screening centers in outpatient waiting areas of the public hospital serving inner-city residents, the city jail, clinics serving the homeless, and with outreach teams in neighborhoods frequented by drug users. All services were provided free. A total of 7,246 persons participated in tuberculin testing; 4,701 (65%) adhered with skin test reading, 809 (17%) had a positive test, 409 (50%) fit current guidelines for isoniazid preventive therapy, 84 (20%) we intended to treat completed therapy. The major limitations of this community-based tuberculin screening and preventive therapy project were the low proportion of infected individuals who were eligible for isoniazid preventive therapy and the poor adherence with a complete regimen among those we intended to treat. For community-based programs to be efficacious, preventive therapy regimens that are of shorter duration and safe for older persons will need to be implemented.     

定量药理学:一个促进药物开发及转换型研究严谨思考的多学科领域

尽管从事定量药理学研究的科学工作者一再强调将定量分析的原则应用于促进新药研发的决策, 定量药理学的发展还是超过了上述领域。普通研究和决策领域总是期望着常规和传统的研究范例发生进步, 当与定量药理学相关的领域自身在发展并与其交互作用时, 自然便产生对临床药理学的协同作用。创新性和可塑性训练计划和策略均是将来临床研究工作中必不可少的要素。掌握定量药理学领域的知识成为对药理科学家的要求, 具有定量药理学背景的人员可望获得更高的薪水。目前定量药理学相关培训计划, 教学资料, 及学术权威均比较贫乏, 学生们可以从企业化、调控性的背景的教师等多种机构的教职员那获得指导, 此外也可以通过在线课程, 可视化教学进修课程, 与他们的导师保持联系。对课程和学位的管理可以采取灵活的态度, 这样可在短期内培养更多的定量药理学工作者。     

Biomechanics of human common carotid artery and design of novel hybrid textile compliant vascular grafts

Entorhinal cortex lesion (ECL) leads to anterograde degeneration of perforant path axons and is known to induce a rapid and intense reaction of astrocytes and microglial cells in the deafferented dentate gyrus. Phagocytosis of degenerating axons involves the establishment and maintenance of cell-matrix and cell-cell interactions by activated glial cells. It was thus our aim to investigate whether the process of axon phagocytosis is accompanied by the expression of adhesion molecules on activated microglial cells or reactive astrocytes, as such molecules mediate bot cell-matrix and cell-cell interactions. We found that the integrin adhesion molecules leukocyte function antigen-1 (LFA-1), very late antigen-4 (VLA-4), and the ligand for LFA-1, intercellular adhesion molecule-1 (ICAM-1), were expressed on microglial cells accumulating in the outer molecular layer of the deafferented dentate gyrus. This upregulation of adhesion molecule expression on microglial cells showing morphological criteria of activation occurred rapidly following ECL, reached its peak at 3 days post lesion (dpl), and gradually returned to control levels after 9 dpl. Astrocytes were never labeled by antibodies directed against these adhesion molecules. Prelabeling of the perforant path with a fluorescent tracer and subsequent ECL led to phagocytosis of fluorescent-labeled axonal debris by cells that were located in the outer molecular layer and showed typical microglial morphology. Double-fluorescence labeling demonstrated that microglial cells engaged in the phagocytosis of axonal debris expressed LFA-1, VLA-4, and the LFA-1-ligand ICAM-1. In conclusion, our results demonstrate that anterograde degeneration of perforant path axons results in adhesion molecule expression on activated microglial cells engaged in axon phagocytosis. The expression of such molecules could represent a mechanism that retains activated microglia in areas of axonal degeneration and perhaps enables the interaction of microglial cells with each other or with other immunocompetent cells.     

Import of cytochrome b2 to the mitochondrial intermembrane space: the tightly folded heme-binding domain makes import dependent upon matrix ATP

Cytochrome b2 is synthesized as a precursor in the cytoplasm and imported to the intermembrane space of yeast mitochondria. We show here that the precursor contains a tightly folded heme-binding domain and that translocation of this domain across the outer membrane requires ATP. Surprisingly, it is ATP in the mitochondrial matrix rather than external ATP that drives import of the heme-binding domain. When the folded structure of the heme-binding domain is disrupted by mutation or by urea denaturation, import and correct processing take place in ATP-depleted mitochondria. These results indicate that (1) cytochrome b2 reaches the intermembrane space without completely crossing the inner membrane, and (2) some precursors fold outside the mitochondria but remain translocation-competent, and import of these precursors in vitro does not require ATP-dependent cytosolic chaperone proteins.