Clonal analysis of a human antibody response. Quantitation of precursors of antibody-producing cells and generation and characterization of monoclonal IgM, IgG, and IgA to rabies virus.

We quantitated and characterized the changes in the human B cell repertoire, at the clonal level, before and after immunization with rabies virus. Moreover, we generated 10 monoclonal cell lines producing IgM, IgG, and IgA antibodies to the virus. We found that in healthy subjects, not previously exposed to the virus, nearly 2% of the circulating B lymphocytes were committed to the production of antibodies that bound the virus. These B cells expressed the surface CD5 molecule. The antibodies they produced were polyreactive IgM that displayed a relatively low affinity for the virus components (Kd, 1.0-2.4 x 10(-6) g/microliters). After immunization, different anti-virus (IgG and IgA) antibody-producing cells consistently appeared in the circulation and increased from less than 0.005% to greater than 10% of the total B cells committed to the production of IgG and IgA, respectively. Most of such B cells do not express CD5 and produce monoreactive antibodies of high affinity for rabies virus (Kd, 6.5 x 10(-9) to 1.2 x 10(-10) g/microliters). One of these IgG mAbs efficiently neutralized rabies virus in vitro and in vivo, as detailed elsewhere (Dietzschold, B., P. Casali, Y. Ueki, M. Gore, C. E. Rupprecht, A. L. Notkins, and H. Koprowski, manuscript submitted for publication). Hybridization experiments using probes specific for the different human V gene segment families revealed that cell precursors producing low affinity IgM binding to rabies virus utilized a restricted number of VH gene segments (i.e., only members of the VHIIIb subfamily), whereas cell precursors producing high affinity IgG and IgA to rabies virus utilized an assortment of different VH gene segments (i.e., members of the VHI, VHIII, VHIV, and VHVI families and VHIIIb subfamily). In conclusion, our studies show that EBV transformation in conjunction with limiting dilution technology and somatic cell hybridization techniques are useful methods for quantitating, at the B cell clonal level, the human antibody response to foreign Ags and for generating human mAbs of predetermined specificity and high affinity

Realistic theory of electromagnetically-induced transparency and slow light in a hot vapor of atoms undergoing collisions

We present a realistic theoretical treatment of a three-level $\Lambda$ system in a hot atomic vapor interacting with a coupling and a probe field of arbitrary strengths, leading to electromagnetically-induced transparency and slow light under the two-photon resonance condition. We take into account all the relevant decoherence processes including col5Blisions. Velocity-changing collisions (VCCs) are modeled in the strong collision limit effectively, which helps in achieving optical pumping by the coupling beam across the entire Doppler profile. The steady-state expressions for the atomic density-matrix elements are numerically evaluated to yield the experimentally measured response characteristics. The predictions, taking into account a dynamic rate of influx of atoms in the two lower levels of the $\Lambda$, are in excellent agreement with the reported experimental results for $^4$He*. The role played by the VCC parameter is seen to be distinct from that by the transit time or Raman coherence decay rate

Observation of slow light in the noise spectrum of a vertical external cavity surface emitting laser

The role of coherent population oscillations is evidenced in the noise spectrum of an ultra-low noise lasers. This effect is isolated in the intensity noise spectrum of an optimized single-frequency vertical external cavity surface emitting laser. The coherent population oscillations induced by the lasing mode manifest themselves through their associated dispersion that leads to slow light effects probed by the spontaneous emission present in the non-lasing side modes.Comment: accepted for publication in Phys. Rev. Let

Use of chromium picolinate and biotin in the management of type 2 diabetes: an economic analysis

This paper addresses the potential economic benefits of chromium picolinate plus biotin (Diachrome ®) use in people with Type 2 diabetes (T2DM). The economic model was developed to estimate the impact on health care systems’ costs by improved HbA1C levels with chromium picolinate plus biotin (Diachrome). Lifetimes cost savings were estimated by adjusting a benchmark from the literature, using a price index to adjust for inflation. The cost of diabetes is highly dependent on the HbA1C level with higher initial levels and higher annual increments increasing the cost. Improvement in glycemic control has proven to be cost-effective in delaying the onset and progression of T2DM, reducing the risk for diabetes-associated complications and lowering utilization and cost of care. Chromium picolinate plus biotin (Diachrome) showed greater improvement of glycemic control in poorly controlled T2DM patients (HbA1C \u3e=10%) compared to their better controlled counterparts (HbA1C \u3c 10%). This improvement was additive to that achieved by oral hypoglycemic medications and correlates to calculated levels of cost savings. Average 3-year cost savings for chromium picolinate plus biotin (Diachrome) use could range from $1,636 for a poorly controlled patient with diabetes without heart diseases or hypertension, to$5,435 for a poorly controlled patient with diabetes, heart disease, and hypertension. Average 3-year cost savings was estimated to be between $3.9 billion and$52.9 billion for the 16.3 million existing patients with diabetes. Chromium picolinate plus biotin (Diachrome) use among the 1.17 million newly diagnosed patients with T2DM each year could deliver lifetime cost savings of $42 billion, or$36,000 per T2DM patient. Affordable, safe, and convenient, chromium picolinate plus biotin (Diachrome) could prove to be a cost-effective complement to existing pharmacological therapies for controlling T2DM. (Disease Management 2005;8:265–275

Multichip imager with improved optical performance near the butt region

A compound imager consists of two or more individual chips, each with at least one line array of sensors thereupon. Each chip has a glass support plate attached to the side from which light reaches the line arrays. The chips are butted together end-to-end to make large line arrays of sensors. Because of imperfections in cutting, the butted surfaces define a gap. Light entering in the region of the gap is either lost or falls on an individual imager other than the one for which it is intended. This results in vignetting and/or crosstalk near the butted region. The gap is filled with an epoxy resin or other similar material which, when hardened, has an index of referaction near that of the glass support plate

An optimally concentrated Gabor transform for localized time-frequency components

Gabor analysis is one of the most common instances of time-frequency signal analysis. Choosing a suitable window for the Gabor transform of a signal is often a challenge for practical applications, in particular in audio signal processing. Many time-frequency (TF) patterns of different shapes may be present in a signal and they can not all be sparsely represented in the same spectrogram. We propose several algorithms, which provide optimal windows for a user-selected TF pattern with respect to different concentration criteria. We base our optimization algorithm on $l^p$-norms as measure of TF spreading. For a given number of sampling points in the TF plane we also propose optimal lattices to be used with the obtained windows. We illustrate the potentiality of the method on selected numerical examples

A scalable optical detection scheme for matter wave interferometry

Imaging of surface adsorbed molecules is investigated as a novel detection method for matter wave interferometry with fluorescent particles. Mechanically magnified fluorescence imaging turns out to be an excellent tool for recording quantum interference patterns. It has a good sensitivity and yields patterns of high visibility. The spatial resolution of this technique is only determined by the Talbot gratings and can exceed the optical resolution limit by an order of magnitude. A unique advantage of this approach is its scalability: for certain classes of nano-sized objects, the detection sensitivity will even increase significantly with increasing size of the particle.Comment: 10 pages, 4 figure

Empirical Study of Carbon Dioxide Released to the Atmosphere during Commercial Red Grape Fermentation

Carbon dioxide (CO2) is a pollutant (greenhouse gas) that is emitted during winemaking but not currently regulated by the Environmental Protection Agency. While winery CO2 emissions have been modeled, they have never been measured continuously or confirmed during a commercial fermentation. As international interest increases in greenhouse gases, it is important to know the amount of CO2 release and the determining factors; yeast strain, temperature, and dissolved CO2 are potentially important parameters. The study was designed to quantify emissions and test a theoretical model for atmospheric release of CO2 during alcoholic fermentation in a commercial winery. Gas release was channeled through a manifold system with an in-line mass flow meter calibrated for CO2, providing real-time and integrated measurement of atmospheric emission. Intermittent use of a hot-wire anemometer was used as a check on the mass-flow measurements. Initial results indicate that integrated mass of CO2 release is dependent on total Brix decrease and not duration of fermentation, consistent with the Williams and Boulton model. However, the time course of release and the shape of the release curves differed substantially among ferments and were primarily dependent on the length of active fermentation