The Future IS Organization in a Flat World

ABSTRACT

The business world is becoming increasingly “flat” with regard to access to global markets and a global workforce. New operational priorities are emerging that require new IS capabilities. The linkage between these operational shifts and the changes required by an IS organization to develop new IS capabilities for a flattening world are identified and discussed.     

K-winner networks.

A special class of mutually inhibitory networks is analyzed, and parameters for reliable K-winner performance are presented. The network dynamics are modeled using interactive activation, and results are compared with the sigmoid model. For equal external inputs, network parameters that select the units with the larger initial activations (the network converges to the nearest stable state) are derived. Conversely, for equal initial activations, networks that select the units with larger external inputs (the network converges to the lowest energy stable state) are derived. When initial activations are mixed with external inputs, anomalous behavior results. These discrepancies are analyzed with several examples. Restrictions on initial states are derived which ensure accurate K-winner performance when unequal external inputs are used.     

Effects of phentermine on responding maintained under multiple fixed-ratio schedules of food and cocaine presentation in the rhesus monkey

Drugs that decrease drug-maintained responding at doses that do not decrease other behaviors in animals may be suitable candidates for development as medications to treat drug abuse in humans. The present study examined whether this effect could be obtained with phentermine, a drug that has been reported to decrease cocaine intake in humans. Rhesus monkeys were trained under multiple fixed-ratio 30-response schedules of food and i.v. cocaine delivery. Phentermine was always given as a slow, i.v. infusion. Acute treatment with phentermine (0.3-10 mg/kg) decreased cocaine-maintained responding at doses that did not decrease, or decreased less, food-maintained responding for each of three unit doses of cocaine (10-100 microg/kg/injection). Subacute treatment with phentermine (3 or 5.6 mg/kg, daily) also decreased cocaine-maintained responding more than food-maintained responding. After subacute treatment was terminated, rates of cocaine-maintained responding generally recovered to levels comparable to those seen during untreated control sessions. Phentermine (0.3-3 mg/kg) did not generally increase responding associated with a very low (1 microg/kg/injection) unit dose of cocaine, suggesting that the decrease in cocaine-maintained responding at higher unit doses was not the result of a leftward shift in the cocaine unit dose-effect function. Phentermine (0.1-3 mg/kg) decreased responding maintained by 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl] piperazine (GBR 12909) (30 microg/kg/injection) at doses similar to those that decreased food-maintained responding. These results show that phentermine is effective in decreasing cocaine self-administration and suggest that it may be an effective medication for cocaine abuse.     

Study of the Transit-Time Limitations of the Impulse Response in Mid-Wave Infrared HgCdTe Avalanche Photodiodes

The impulse response in frontside-illuminated mid-wave infrared HgCdTe electron avalanche photodiodes (APDs) has been measured with localized photoexcitation at varying positions in the depletion layer. Gain measurements have shown an exponential gain, with a maximum value of M = 5000 for the diffusion current at a reverse bias of V _b = 12 V. When the light was injected in the depletion layer, the gain was reduced as the injection approached the N+ edge of the junction. The impulse response was limited by the diode series resistance–capacitance product, RC, due to the large capacitance of the diode metallization. Hence, the fall time is given by the RC constant, estimated as RC = 270 ps, and the rise time is due to the charging of the diode capacitance via the transit and multiplication of carriers in the depletion layer. The latter varies between t _10–90 = 20 ps (at intermediate gains M < 500) and t _10–90 = 70 ps (at M = 3500). The corresponding RC-limited bandwidth is BW = 600 MHz, which yields a new absolute record in gain–bandwidth product of GBW = 2.1 THz. The increase in rise time at high gains indicates the existence of a limit in the transit-time-limited gain–bandwidth product, GBW = 19 THz. The impulse response was modeled using a one-dimensional deterministic model, which allowed a quantitative analysis of the data in terms of the average velocity of electrons and holes. The fitting of the data yielded a saturation of the electron and hole velocity of v _e = 2.3 × 10⁷ cm/s and v _h = 1.0 × 10⁷ cm/s at electric fields E > 1.5 kV/cm. The increase in rise time at high bias is consistent with the results of Monte Carlo simulations and can be partly explained by a reduction of the electron saturation velocity due to frequent impact ionization. Finally, the model was used to predict the bandwidth in diodes with shorter RC = 5 ps, giving BW = 16 GHz and BW = 21 GHz for x _j = 4 μm and x _j = 2 μm, respectively, for a gain of M = 100.     

Orbital trauma

To study factors influencing the distribution of local anaesthetics in the subarachnoid space, an in vitro model is constructed which takes into account the natural curvature of the spinal column and the volume occupation of spinal cord and nerve fibres to resemble the in vivo situation. Three Marcaine solutions of different baricity (1003, 1008, 1030 kg/m3) are injected with a 22 G, a 27 G Quincke point needle and a 18 G multiport catheter into three models of non-pathological spinal columns with injection flow speeds of 0.6, 0.2 or 0.1 ml/s. Methylene blue is added for visual and qualitative assessment of drug distribution. Baricity is the main actor in the spreading of the drug solution. For all other variables, no significant difference is found after ten minutes, though the initial distribution may differ according to the geometry used. A hypobaric solution yields a remarked difference between fast and slower injections. The position of the catheter should be controlled.     

The effect of FMRFamide analogs on [35S]GTP-gamma-S stimulation in squid optic lobes

Pharmacological study of Phe-Met-Leu-Phe-amide (FMRFa) receptors is hindered by the lack of selective ligands. The classification of these selective ligands is further hampered by the limited availability of functional assays. In this study, we evaluated several synthetic FMRFa analogs for agonist and antagonist activity by measuring their abilities to produce [35-S]-GTP-gamma-S stimulation or to inhibit FMRFa-induced [35S]-GTP-gamma-S binding in squid optic lobes. Analogs included acetyl-Phe-norLeu-Arg-Phe-amide (acFnLRFa), desamino-Tyr-Phe-Leu-Arg-amide (daYFLRa), desamino Tyr-Phe-norLeu-Arg-Phe-amide (daYFnLRFa), desamino Tyr-Phe-norLeu-Arg-[TIC]-amide (daYFnLR[TIC]a), desamino Tyr-Trp-norLeu-Arg-amide (daYWnLRa), (D)-Tyr-Phe-norLeu-Arg-Phe-amide (D)-YFnLRFa), Phe-Leu-Arg-Phe-amide (FLRFa), and the D-amino acid analogs of FMRFa (D-FMRFa, F-(D)-MRFa and FM-(D)-RFa). For agonist studies, full dose-response curves were generated and analyzed for potency and efficacy (maximal percent effect). FMRFamide as well as analogs ac-FnLRFa, daYFnLRFa, daYFnLR[TIC]a, D-YFnLRFa, FLRFa, and (D)-FMRFa stimulated [35S]-GTP-gamma-S binding. Analogs daYWnLRa, daYFLRa, F-(D)-MRFa, and FM-(D)-RFa failed to stimulate either [35S]-GTP-gamma-S binding or to inhibit FMRFa-induced [35S]-GTP-gamma-S binding. The rank order of potency was daYFnLRFa > or = daYFnLRF[TIC]a > acFnLRFa > (D)YFnLRFa > FLRFa > or = FMRFa > (D)-FMRFa. The order of efficacy was daYFnLRFa = acFnLRFa = (D)-YFnLRFa > FLRFa = FMRFa > or = (D)-FMRFa > or = daYFnLRF[TIC]a. Peptide analog daYFnLR[TIC]a was less efficacious (59% maximal stimulation) than analogs daYFnLRFa, acFnLRFa, and (D)-YFnLRFa (113-146% maximal stimulation). A maximal concentration of daYFnLR[TIC]a (10 microM) reduced daYFnLRFa, acFnLRFa, and (D)-YFnLRFa induced [35S]-GTP-gamma-S stimulation, indicating that daYFnLR[TIC]a is a partial agonist at the receptor stimulated by the FMRFamide analogs. Analysis of the structural requirements needed for promoting [35S]-GTP-gamma-S binding show that elongation (i.e., daYFnLRFa, D-YFnLRFa) or modification of Phe1 (ac-FnLRFa) leads to increased efficacy and potency. Moreover, elimination of the C-terminal Phe (daYWnLRa, daYFLRa,) leads to a loss of biological activity. However, substitution with L-1,2,3,4 tetrahydroisoquinoline-3-carboxylic acid, a rigid analog of the C-terminal Phe (daYFnLR[TIC]a), leads to decreased efficacy but not loss of potency. The data suggest that immobilization or modification of the C-terminal Phe may produce highly selective and potent FMRFamide antagonists. These results agree with published receptor radioligand studies and indicate that the [35S]GTP-gamma-S assay may be useful in classifying novel FMRFamide-selective ligands.