Patients with schizophrenia often display unusual language impairments. This is a wide ranging critical review of the literature on language in schizophrenia since the 19th century. We survey schizophrenic language level by level, from phonetics through phonology, morphology, syntax, semantics, and pragmatics.There are at least two kinds of impairment (perhaps not fully distinct): thought disorder, or failure to maintain a discourse plan, and schizophasia, comprising various dysphasia-like impairments such as clanging, neologism, and unintelligible utterances.Thought disorder appears to be primarily a disruption of executive function and pragmatics, perhaps with impairment of the syntax-semantics interface; schizophasia involves disruption at other levels. Phonetics is also often abnormal (manifesting as flat intonation or unusual voice quality), but phonological structure, morphology, and syntax are normal or nearly so (some syntactic impairments have been demonstrated). Access to the lexicon is clearly impaired, manifesting as stilted speech, word approximation, and neologism. Clanging (glossomania) is straightforwardly explainable as distraction by self-monitoring.Recent research has begun to relate schizophrenia, which is partly genetic, to the genetic endowment that makes human language possible. D
An electrodeposition process for void-free bottom-up filling of sub-millimeter scale through silicon vias (TSVs) with Cu is detailed. The 600 μm deep and nominally 125 μm diameter metallized vias were filled with Cu in less than 7 hours under potentiostatic control. The electrolyte is comprised of 1.25 mol/L CuSO 4 −0.25 mol/L CH 3 SO 3 H with polyether and halide additions that selectively suppress metal deposition on the free surface and side walls. A brief qualitative discussion of the procedures used to identify and optimize the bottom-up void-free feature filling is presented.
There is considerable interest in the oxidative fate of phenols such as p-cresol as environmental pollutants and uremic toxins. We supply a menu of spectroscopic options for the high throughput screening of laccase oxidation of p-cresol through multiple modes of detection. Laccase activity was monitored kinetically at pH 4.5 by absorption changes at 250 nm, 274 nm or 297 nm, and in endpoint mode by the bathochromic shift in absorption to 326 nm in 50 mM NaOH. Laccase oxidation of p-cresol was also detected by product fluorescence at 425 nm after excitation at 262 nm or 322 nm in 50 mM NaOH. We optimized the kinetic parameters for p-cresol oxidation (pH optimum 4.5-5.1; 37 degrees C; Km = 2.2 mM) resulting in laccase limits of detection and quantitation of 25 pg/microL and 75 pg/microL, respectively (approximately 360 pM; 25 ppb). The sensitivity for p-cresol was similar to previously reported values. The small (approximately 20%) decrease in signal strength after six cycles of excitation over a 3 h period was attributed to photobleaching or photodegradation of the emitter and not due to fluorescence decay (photoinstability). Halide inhibition was characteristic of laccases (IC(50) = 25 mM NaCl). A unique advantage of our assay is that laccase catalysis could be interrogated using multi-mode absorption or fluorescence under acidic or basic conditions, in real time or endpoint modes. Orthogonal interrogation facilitates ratiometric analysis enabling high specificity while minimizing interferences during compound library screening. The phenolic alcohol p-cresol may be a model for monolignol oxidation. Our studies might find applications in biofuels, to triage dialysis patients, or for the environmental bioremediation of phenols.
Noncovalent forces are involved in the supramolecular selfassembly. [1][2][3][4] We previously showed that a class of chromophores known as cyanines were capable of spontaneously selfassembling upon a variety of biopolymers including carbohydrates. [5][6][7][8] Cyanines are photosensitive dyes composed of two quaternized, nitrogen-containing, and heterocyclic ring structures, that are linked by a polymethine bridge. 9 Cyanines are characterized by high molar absorptivity, low intrinsic fluorescence and large fluorescence enhancement following self-assembly upon various templates. Supramolecular selfassembly involves reversible, noncovalent, and electrostatic (coulombic) interactions including hydrogen and/or charge bonding, van der Waals and hydrophobic forces. Cyanine selfassembly is sometimes accompanied by strong, sharp and bathochromic fluorescence, characteristic of J-aggregates. 10Cyanines are also capable of forming hypsochromic, nonfluorescent or very weakly fluorescent H-aggregates. 10 Controlling and tuning the supramolecular self-assembly processes will offer insights to enable programmability to achieve desired functional nanomaterials. We therefore further investigated the self-assembling of cyanines from our molecular "library" in order to identify a chromophore that was capable of forming intensely fluorescent J-aggregates.Our objectives were: 1) Identify cyanine chromophores from our molecular library that would be a sensitive probe for nucleic acids; 2) Correlate the form-function aspects of cyanine chemistry to self-assembly on nucleic acid scaffolds; 3) Compare the detection limits of single-stranded viral DNA, double-stranded viral DNA, double-stranded genomic DNA, and RNA, using self-assembly; 4) Optimize detection conditions for nucleic acids based upon supramolecular self-assembly including the stability of the nucleic acids-cyanine complex; and 5) Demonstrate supramolecular self-assembly processes were involved in the aggregation of the cyanine upon nucleic acid scaffolds. Results from these investigations are described in this paper. Experimental Reagents and chemicalsThe chemical structures of various cyanines from our molecular "library" 5,11 are shown in Fig. 1. Stock solutions of cyanines were prepared in methanol and stored refrigerated. Single stranded, circular, fX174 virion DNA (5386 bases, Mr = 1.7 ¥ 10 6 Da) from fX174 am3 cs70 bacteriophage was purchased from New England Biolabs (Ipswich, MA). Greater than 85% of the DNA molecules were circular. The double stranded bacteriophage lDNA composed of 48502 bp (Mr = 3.2 ¥ 10 7 Da) was from Promega (Madison, WI). Unsheared Escherichia coli (E. coli) genomic DNA with an average size of 16 kb (Mr = 1.4 ¥ 10 7 Da) was purchased from Sigma Aldrich (St. Louis, MO). The DNA had been purified by equilibrium buoyant density gradient ultracentrifugation in CsCl and agarose gel (0.8%) electrophoresis was used for size determination. Genomic DNA was dissolved using TE buffer (10 mM Tris-HCl, pH 7.5, 1 mM NaCl and 1 mM EDTA). The DNA solution wa...
A methanesulfonic acid (MSA) electrolyte with a single suppressor additive was used for potentiostatic bottom-up filling of copper in mesoscale through silicon vias (TSVs). Conversly, galvanostatic deposition is desirable for production level full wafer plating tools as they are typically not equipped with reference electrodes which are required for potentiostatic plating. Potentiostatic deposition was used to determine the over-potential required for bottom-up TSV filling and the resultant current was measured to establish a range of current densities to investigate for galvanostatic deposition. Galvanostatic plating conditions were then optimized to achieve void-free bottom-up filling in mesoscale TSVs for a range of sample sizes.
We present a miniaturized high-throughput sensor array that will augment biofuel technology by facilitating in situ biochemical measurements upon micrometer-scale surfaces of leaves, stems, or petals. We used semiconductor processing to photopattern Foturan glass wafers and fabricated gold-plated microscopic electrode needles (ElectroNeedles) that pierced 125-mum-thick surfaces without deformation. The 5 x 5 or 10 x 10 arrays of ElectroNeedles can analyze 25 or 100 samples simultaneously, increasing throughput. Each microneedle in the array can also be individually addressed and selectively functionalized using diazonium electrodeposition, conferring multiplexing capability. Our microfabrication is a simple, inexpensive, and rapid alternative to the time-, cost-, and protocol-intense, deep-reactive-ion-etching Bosch process. We validated the system performance by electrochemically detecting p-cresol, a phenolic substrate for laccase, an enzyme that is implicated in lignin degradation and therefore important to biofuels. Our limits of detection (LOD) and quantization (LOQ) for p-cresol were 1.8 and 16microM, respectively, rivaling fluorescence detection (LOD and LOQ = 0.4 and 3microM, respectively). ElectroNeedles are multiplexed, high-throughput, chip-based sensor arrays designed for minimally invasive penetration of plant surfaces, enabling in situ and point-of-test analyses of biofuel-related biochemicals.
We describe a novel technique that utilizes simultaneous implementation of dielectrophoresis (DEP) and magnetophoresis (MAP) to focus magnetic particles into streams for optical analysis of biological samples. This technique does not require sheath flow and utilizes a novel interdigitated electrode array chip that yields multiple streams of flowing magnetic particles in single-file columns. The MAP force placed particles in close proximity to the microelectrodes where they were subjected to a strong DEP force that generated the particle focusing effect. Particle focusing efficiency was improved using this combination DEP-MAP technique compared to DEP alone: particle stream widths were reduced ∼47% and stream width variability was reduced 80% for focused streams of 8.5 μm diameter magnetic particles. 3 μm diameter magnetic particles were strongly focused with DEP-MAP (∼4 μm wide streams with sub-μm variability in stream width) while DEP alone provided minimal focusing. Additional components of a prototype detection system were also demonstrated including an integrated magnetic pelleting component, a hand-held MHz frequency signal generator and a bench-top near-confocal microscope for optical analysis of flowing particles. Preliminary testing of a sandwich assay performed on the surface of magnetic particles showed 50 ppb detection levels of a surrogate biotoxin (ovalbumin) in a raw milk sample.
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