Disruption of ergosterol biosynthesis,growth, and the morphological transition in <Emphasis Type="Italic">Candida albicans</Emphasis> by sterol methyltransferase inhibitors containing sulfur at C-25 in the sterol side chain

The sterol substrate analog 25-thialanosterol and its corresponding sulfonium salt were evaluated for their ability to serve as antifungal agents and to inhibit sterol methyltransferase (SMT) activity in Candida albicans. Both compounds inhibited cell proliferation, were fungistatic, interrupted the yeastlike-form to germ-tube-form transition, and resulted in the accumulation of zymosterol and related Δ²⁴-sterols concurrent with a decrease in ergosterol, as was expected for the specific inhibition of SMT activity. Feedback on sterol synthesis was evidenced by elevated levels of cellular sterols in treated vs. control cultures. However, neither farnesol nor squalene accumulated in significant amounts in treated cultures, suggesting that carbon flux is channeled from the isoprenoid pathway to the sterol pathway with minor interruption or redirection until blockage at the C-methylation step. Activity assays using solubilized C. albicans SMT confirmed the inhibitors impair SMT action. Kinetic analysis indicated that 25-thialanosterol inhibited SMT with the properties of a time-dependent mechanismbased inactivator K _i of 5 =gmM and apparent k _inact of 0.013 min⁻¹, whereas the corresponding sulfonium salt was a reversible-type transition state analog exhibiting a K _i of 20 nM. The results are interpreted to imply changes in ergosterol homeostasis as influenced by SMT activity can control growth and the morphological transition in C. albicans, possibly affecting disease development.     

Reports of the DAS02 working groups

This document is a collection of four working group reports in the areas of digital libraries, document image retrieval, layout analysis, and Web document analysis. These reports were the outcome of discussions by participants at the Fifth IAPR International Workshop on Document Analysis Systems held in Princeton, NJ on 19-21 August 2002.Published online: 16 March 2004     

Reproductive sequelae in female rats after in utero and neonatal exposure to the phytoestrogen genistein

OBJECTIVE: To determine reproductive sequelae in female rats after in utero and lactational dietary exposure to genistein. DESIGN: Experimental animal study. SETTING: University laboratory. ANIMAL(S): Sprague Dawley rats. INTERVENTION(S): Pregnant rats were fed control rat chow or rat chow incorporated with genistein (approximately 50 microg/d) beginning on day 17 of gestation and continuing until the end of lactation (postpartum day 21). Genistein-exposed female pups were divided into two groups on day 21. One group continued to receive a genistein-added diet (G70); the other group was changed to a control diet (Ex-G). At necropsy (days 21 and 70), blood and reproductive tissues were collected. MAIN OUTCOME MEASURE(S): Serum levels of gonadotropins and gonadal steroids and histopathologic examination of the ovaries. RESULT(S): The weight of the ovaries and uterus and serum levels of E2 and progesterone in genistein-exposed rats on day 21 (G21) were significantly reduced compared with control rats. On day 70, serum levels of E2, progesterone, LH, and FSH were similar in all groups. Atretic follicles and secondary interstitial glands were more common in G70 and Ex-G rats compared with control rats. Cystic rete ovarii was observed in some G70 and Ex-G rats. CONCLUSION(S): Our data indicate that in utero and lactational exposure to dietary genistein adversely affects reproductive processes in the adult female rat.     

5-GHz 32-bit integer execution core in 130-nm dual-V/sub T/ CMOS

A 32-bit integer execution core containing a Han-Carlson arithmetic-logic unit (ALU), an 8-entry /spl times/ 2 ALU instruction scheduler loop and a 32-entry /spl times/ 32-bit register file is described. In a 130 nm six-metal, dual-V/sub T/ CMOS technology, the 2.3 mm/sup 2/ prototype contains 160 K transistors. Measurements demonstrate capability for 5-GHz single-cycle integer execution at 25/spl deg/C. The single-ended, leakage-tolerant dynamic scheme used in the ALU and scheduler enables up to 9-wide ORs with 23% critical path speed improvement and 40% active leakage power reduction when compared to a conventional Kogge-Stone implementation. On-chip body-bias circuits provide additional performance improvement or leakage tolerance. Stack node preconditioning improves ALU performance by 10%. At 5 GHz, ALU power is 95 mW at 0.95 V and the register file consumes 172 mW at 1.37 V. The ALU performance is scalable to 6.5 GHz at 1.1 V and to 10 GHz at 1.7 V, 25/spl deg/C.     

Style context with second-order statistics

Patterns often occur as homogeneous groups or fields generated by the same source. In multisource recognition problems, such isogeny induces statistical dependencies between patterns (termed style context). We model these dependencies by second-order statistics and formulate the optimal classifier for normally distributed styles. We show that model parameters estimated only from pairs of classes suffice to train classifiers for any test field length. Although computationally expensive, the style-conscious classifier reduces the field error rate by up to 20 percent on quadruples of handwritten digits from standard NIST data sets.     

Experimental and numerical prediction of effect of frequency on bending fatigue performance of polyamide 66/hectorite nanocomposite

An increased use of thermoplastics in components and structures that are subjected to cyclic loads necessitates a specific attention to variables that affect the hysteretic heating. Hysteretic heating effect in polyamide 66/hectorite nanocomposite has been investigated under bending strain control mode using a custom-built bending fatigue test setup in a laboratory environment. Dynamic mechanical analysis (DMA) results revealed a considerable rise in loss modulus with a decrease in frequency from 1 to 0.1?Hz irrespective of the temperature of the specimen. Alternatively, a reduction in fatigue test frequency from 2 to 0.5?Hz resulted in a significant decrease in cyclic softening. Fatigue behaviour predicted from DMA results using coupled structural/thermal finite element analysis is fairly in agreement with the experimental one. An accelerated crack initiation at decreased specimen temperature and high cyclic steady state stress reduced the fatigue life at 0.5?Hz compared with 2?Hz.     

Mechanics and chemistry: single molecule bond rupture forces correlate with molecular backbone structure

We simultaneously measure conductance and force across nanoscale junctions. A new, two-dimensional histogram technique is introduced to statistically extract bond rupture forces from a large data set of individual junction elongation traces. For the case of Au point contacts, we find a rupture force of 1.4 ± 0.2 nN, which is in good agreement with previous measurements. We then study systematic trends for single gold metal-molecule-metal junctions for a series of molecules terminated with amine and pyridine linkers. For all molecules studied, single molecule junctions rupture at the Au-N bond. Selective binding of the linker group allows us to correlate the N-Au bond-rupture force to the molecular backbone. We find that the rupture force ranges from 0.8 nN for 4,4' bipyridine to 0.5 nN in 1,4 diaminobenzene. These experimental results are in excellent quantitative agreement with density functional theory based adiabatic molecular junction elongation and rupture calculations.     

Attainable regions of reactive distillation—Part III. Complex reaction scheme: Van de Vusse reaction

The main underlying principle behind the application of reactive distillation (RD) for selectivity enhancement is to facilitate the separation of selected components and favorably manipulate the composition profiles in the reactive zone to expedite the desired reaction. In this paper, a geometric approach of attainable region (AR), which is already developed for conventional reactor network, is extended further to include few representative RD configurations. We define new RD building blocks and the corresponding composition vectors that indicate a need of networking of RD units among themselves and with conventional reactors to enlarge the set of attainable compositions. A model reaction scheme of van de Vusse type ) is studied as an illustrative example and an algorithm is developed to obtain the attainable region for the given kinetics, feed composition and relative volatilities. In almost all the different cases, which are studied by varying the kinetics and volatility pattern, network consisting of RD units performs better than the conventional reactor network.     

Dissecting contact mechanics from quantum interference in single-molecule junctions of stilbene derivatives

Electronic factors in molecules such as quantum interference and cross-conjugation can lead to dramatic modulation and suppression of conductance in single-molecule junctions. Probing such effects at the single-molecule level requires simultaneous measurements of independent junction properties, as conductance alone cannot provide conclusive evidence of junction formation for molecules with low conductivity. Here, we compare the mechanics of the conducting para-terminated 4,4'-di(methylthio)stilbene and moderately conducting 1,2-bis(4-(methylthio)phenyl)ethane to that of insulating meta-terminated 3,3'-di(methylthio)stilbene single-molecule junctions. We simultaneously measure force and conductance across single-molecule junctions and use force signatures to obtain independent evidence of junction formation and rupture in the meta-linked cross-conjugated molecule even when no clear low-bias conductance is measured. By separately quantifying conductance and mechanics, we identify the formation of atypical 3,3'-di(methylthio)stilbene molecular junctions that are mechanically stable but electronically decoupled. While theoretical studies have envisaged many plausible systems where quantum interference might be observed, our experiments provide the first direct quantitative study of the interplay between contact mechanics and the distinctively quantum mechanical nature of electronic transport in single-molecule junctions.     

The effect of nano-sized sintering aids on toughening behavior of silicon nitride

Processing plays an important role in determining the microstructure of silicon nitrides which in turn influences the mechanical properties, such as hardness and toughness. Sintering aids are an important processing parameter. The influence of the chemistry of sintering aids on properties of silicon nitrides is a well-explored subject. Here the size of sintering aids used and its impact on microstructure and mechanical properties is explored. Specifically the use of nano-scale versus micron-scale sintering aids is examined. Microstructures and mechanical properties for silicon nitrides hot-pressed with nano-sized sintering aids are compared with a reference silicon nitride hot-pressed with micron-sized sintering aids. Hardness and fracture toughness are determined at room temperature using hardness indents. Grain size and aspect ratio distributions are determined for the two silicon nitrides and their impact on mechanical properties are examined. Toughening behavior is studied by experimentally determining R-curves. Both toughness and toughening (R-curve) behavior are shown to improve with the use of nano-scale sintering aids.