Sweet Fairytale: Carbohydrates as Backbones for Glyconanomedicine

The use of nanoparticles (NPs) in medical applications is rapidly growing, with more than 30 NP-based drugs approved for clinical use. Different building blocks are used to generate NPs for drug and imaging delivery tasks. Among them, carbohydrates represent an exciting option that is currently being exploited in vivo and in clinical trials. Carbohydrates have excellent biocompatibility, biodegradability, low toxicity, and low cost. In addition, the ease of chemical modification enables the preparation of a wide collection of NPs for a variety of tasks. Here, we will describe the properties of common carbohydrates and the main mechanisms for carbohydrates-based NP preparation and discuss several key concepts from the physicochemical and structural features of NP-based carbohydrates for pre-clinical and clinical applications.     

Understanding attitudes toward affirmative action programs in employment: Summary and meta-analysis of 35 years of research.

Affirmative action programs (AAPs) are controversial employment policies in the United States and elsewhere. A large body of evidence about attitudinal reactions to AAPs in employment has accumulated over 35 years: at least 126 independent samples involving 29,000 people. However, findings are not firmly established or integrated. In the current article, the authors summarize and meta-analytically estimate relationships of AAP attitudes with (a) structural features of such programs, (b) perceiver demographic and psychological characteristics, (c) interactions of structural features with perceiver characteristics, and (d) presentation of AAP details to perceivers, including justification of the AAP. Results are generally consistent with predictions derived from self-interest considerations, organizational justice theory, and racism theories. They also suggest practical ways in which AAPs might be designed and communicated to employees to reduce attitudinal resistance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired Functional Connectivity Underlies Fragile X Syndrome

Fragile X syndrome (FXS), the most common form of inherited intellectual disability, is caused by a developmentally regulated silencing of the FMR1 gene, but its effect on human neuronal network development and function is not fully understood. Here, we isolated isogenic human embryonic stem cell (hESC) subclones—one with a full FX mutation and one that is free of the mutation (control) but shares the same genetic background—differentiated them into induced neurons (iNs) by forced expression of NEUROG-1, and compared the functional properties of the derived neuronal networks. High-throughput image analysis demonstrates that FX-iNs have significantly smaller cell bodies and reduced arborizations than the control. Both FX- and control-neurons can discharge repetitive action potentials, and FX neuronal networks are also able to generate spontaneous excitatory synaptic currents with slight differences from the control, demonstrating that iNs generate more mature neuronal networks than the previously used protocols. MEA analysis demonstrated that FX networks are hyperexcitable with significantly higher spontaneous burst-firing activity compared to the control. Most importantly, cross-correlation analysis enabled quantification of network connectivity to demonstrate that the FX neuronal networks are significantly less synchronous than the control, which can explain the origin of the development of intellectual dysfunction associated with FXS.     

Two-month-old infants' sensitivity to changes in arbitrary syllable–object pairings: The role of temporal synchrony.

To explore early lexical development, the authors examined infants' sensitivity to changes in spoken syllables and objects given different temporal relations between syllable–object pairings. In Experiment 1, they habituated 2-month-olds to 1 syllable, /tah/ or /gah/, paired with an object in synchronous (utterances coincident with object motions, N = 16) or asynchronous (utterances erratic relative to object motions, N = 16) conditions. In the asynchronous condition, the audio track preceded or succeeded the visual track by 1,200 ms. On test, infants in the synchronous condition alone detected the changes. Post hoc computational analyses confirmed lower time separation, interpreted as greater synchrony, between peaks and onsets–offsets of visual motion and audio energy in the synchronous relative to the asynchronous condition. Further examining lexical development, in Experiment 2 they habituated 2-month-olds (N = 16) to two synchronous syllable–object pairs and tested them on switch versus same pairings. Infants failed to detect the switch in the pairings. These results suggest that 2-month-olds use synchrony to detect changes in one novel syllable–object pairing at a time, providing a basis for further word mapping development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multi-identity planning process in a studio course: Integrative planning in multi-identity environments

The planning process in a planning studio demonstrates a microcosm of diverse concepts of ideologies and identities seeking acknowledgment and spatial recognition.In the modern world of multiple and dynam icidentities and ideologies,aspiring for the self-recognition of regions, towns, and communities, aplace-based identity has become a core aspect that needs to be taken into planning consideration.The analytic planning method used is iterative of both top–down and bottom–up approaches,thereby creating multi-dimension and coherent planning alternatives where spatial solutions arise from communities along theirc hanging processes.We present two spatialal ternative plans that were developed in the studio course and are based on this line of thinking. Results were very dynamic aspiring complex plans, which are also highly applicable and flexible, thereby addressing a wide range of ideologies and identities.     

Extracting maximal information about sets of minimum cuts

There are two well-known, elegant, compact, and efficiently computed representations of selected minimum edge cuts in a weighted, undirected graphG=(V, E) withn nodes andm edges: at one extreme, the Gomory-Hu cut tree [12] represents minimum cuts, one for each pair of nodes inG; at the other extreme, the Picard-Queyranne DAG [24] represents all the minimum cuts between a single pair of nodes inG. The GH cut tree is constructed with onlyn–1 max-flow computations, and the PQ DAG is constructed with one max-flow computation, plusO(m) additional time. In this paper we show how to marry these two representations, getting the best features of both. We first show that we can construct all DAGs, one for each fixed pair of nodes, using onlyn–1 max-flow computations as in [12], plusO(m) time per DAG as in [24]. This speeds up the obvious approach by a factor ofn. We then apply this approach to an unweighted graphG, to find all the edge-connectivity cuts inG, i.e., cuts with capacity equal to the connectivity ofG. Matula [22] gave a method to find one connectivity cut inO(nm) time; we show thatO(nm) time suffices to represent all connectivity cuts compactly, and to list all of them explicitly. This improves the previous best time bound ofO(n ² m) [3] for listing the connectivity cuts. The connectivity cuts are central in network reliability calculations. We then show how to find all pairs of nodes that are separated by at least one connectivity cut inO(nm) time.Research was partially supported by Grant CCR-8803704 from the National Science Foundation.     

Expression and possible involvement of calpain isoforms in mammalian egg activation

At fertilization in mammals, the spermatozoon triggers a unique signal transduction mechanism within the egg, leading to its activation. It is well accepted that the earliest event observed in all activated eggs is an abrupt rise in intracellular calcium concentrations. However, little is known regarding the downstream proteins that are activated by this rise in calcium. Calpains constitute a family of intracellular calcium-dependent cysteine proteases whose members are expressed widely in a variety of cells. We investigated the expression and possible role of the calpain isoforms mu and m throughout egg activation. Both calpains were expressed in the rat egg and localized at the egg cortex as well as in the meiotic spindle. m Calpain translocated to the membrane and to the spindle area during parthenogenetic egg activation and during in vivo fertilization, upon sperm binding to the egg. The cytoskeletal protein alpha-spectrin (fodrin) was proteolysed by calpain during the egg-activation process, as demonstrated by specific calpain-breakdown products. Following parthenogenetic activation by ionomycin or puromycin, the calpain-selective permeable inhibitor, calpeptin, inhibited the resumption of meiosis and cortical reaction in a dose-dependent manner. Calpeptin was also effective in inhibiting in vitro fertilization. These results may imply a correlation between calpain activation and mammalian egg activation at fertilization and a possible role for calpain in the cascade of cellular events leading to resumption of meiosis.