The CD28-Transmembrane Domain Mediates Chimeric Antigen Receptor Heterodimerization With CD28.

Anti-CD19 chimeric antigen receptor (CD19-CAR)-engineered T cells are approved therapeutics for malignancies. The impact of the hinge domain (HD) and the transmembrane domain (TMD) between the extracellular antigen-targeting CARs and the intracellular signaling modalities of CARs has not been systemically studied. In this study, a series of 19-CARs differing only by their HD (CD8, CD28, or IgG <sub>4</sub> ) and TMD (CD8 or CD28) was generated. CARs containing a CD28-TMD, but not a CD8-TMD, formed heterodimers with the endogenous CD28 in human T cells, as shown by co-immunoprecipitation and CAR-dependent proliferation of anti-CD28 stimulation. This dimerization was dependent on polar amino acids in the CD28-TMD and was more efficient with CARs containing CD28 or CD8 HD than IgG <sub>4</sub> -HD. The CD28-CAR heterodimers did not respond to CD80 and CD86 stimulation but had a significantly reduced CD28 cell-surface expression. These data unveiled a fundamental difference between CD28-TMD and CD8-TMD and indicated that CD28-TMD can modulate CAR T-cell activities by engaging endogenous partners

Toward engineering biosystems with emergent collective functions

Many complex behaviors in biological systems emerge from large populations of interacting molecules or cells, generating functions that go beyond the capabilities of the individual parts. Such collective phenomena are of great interest to bioengineers due to their robustness and scalability. However, engineering emergent collective functions is difficult because they arise as a consequence of complex multi-level feedback, which often spans many length-scales. Here, we present a perspective on how some of these challenges could be overcome by using multi-agent modeling as a design framework within synthetic biology. Using case studies covering the construction of synthetic ecologies to biological computation and synthetic cellularity, we show how multi-agent modeling can capture the core features of complex multi-scale systems and provide novel insights into the underlying mechanisms which guide emergent functionalities across scales. The ability to unravel design rules underpinning these behaviors offers a means to take synthetic biology beyond single molecules or cells and toward the creation of systems with functions that can only emerge from collectives at multiple scales

Non-adiabatic charge pump: an exact solution

We derived a general and exact expression of current for quantum parametric charge pumps in the non-adiabatic regime at finite pumping frequency and finite driving amplitude. The non-perturbative theory predicts a remarkable plateau structure in the pumped current due to multi-photon assisted processes in a double-barrier quantum well pump involving only a {\it single} pumping potential. It also predicts a current reversal as the resonant level of the pump crosses the Fermi energy of the leads

Theory of spin-polarized bipolar transport in magnetic p-n junctions

The interplay between spin and charge transport in electrically and magnetically inhomogeneous semiconductor systems is investigated theoretically. In particular, the theory of spin-polarized bipolar transport in magnetic p-n junctions is formulated, generalizing the classic Shockley model. The theory assumes that in the depletion layer the nonequilibrium chemical potentials of spin up and spin down carriers are constant and carrier recombination and spin relaxation are inhibited. Under the general conditions of an applied bias and externally injected (source) spin, the model formulates analytically carrier and spin transport in magnetic p-n junctions at low bias. The evaluation of the carrier and spin densities at the depletion layer establishes the necessary boundary conditions for solving the diffusive transport equations in the bulk regions separately, thus greatly simplifying the problem. The carrier and spin density and current profiles in the bulk regions are calculated and the I-V characteristics of the junction are obtained. It is demonstrated that spin injection through the depletion layer of a magnetic p-n junction is not possible unless nonequilibrium spin accumulates in the bulk regions--either by external spin injection or by the application of a large bias. Implications of the theory for majority spin injection across the depletion layer, minority spin pumping and spin amplification, giant magnetoresistance, spin-voltaic effect, biasing electrode spin injection, and magnetic drift in the bulk regions are discussed in details, and illustrated using the example of a GaAs based magnetic p-n junction.Comment: 36 pages, 11 figures, 2 table

Modulation instability induced by cross-phase modulation in a dual-wavelength dispersion-managed soliton fiber ring laser

We report on the observation of modulation instability induced by cross-phase modulation in a dual-wavelength operation dispersion-managed soliton fiber ring laser with net negative cavity dispersion. The passively mode-locked operation is achieved by using nonlinear polarization rotation technique. A new type of dual-wavelength operation, where one is femtosecond pulse and the other is picosecond pulse operation, is obtained by properly rotating the polarization controllers. When the dual-wavelength pulses are simultaneously circulating in the laser ring cavity, a series of stable modulation sidebands appears in the picosecond pulse spectrum at longer wavelength with lower peak power due to modulation instability induced by cross-phase modulation between the two lasing wavelengths. Moreover, the intensities and wavelength shifts of the modulation sidebands can be tuned by varying the power of the femtosecond pulse or the lasing central wavelengths of the dual-wavelength pulses. The theoretical analysis of the modulation instability induced by cross-phase modulation in our fiber laser is also presented.Comment: 26 pages, 10 figure

Search for Neutral Higgs Bosons of the Minimal Supersymmetric Standard Model in e+e- Interactions at \sqrt{s} = 189 GeV

A search for the lightest neutral scalar and neutral pseudoscalar Higgs bosons in the Minimal Supersymmetric Standard Model is performed using 176.4 pb^-1 of integrated luminosity collected by L3 at a center-of-mass energy of 189 GeV. No signal is observed, and the data are consistent with the expected Standard Model background. Lower limits on the masses of the lightest neutral scalar and pseudoscalar Higgs bosons are given as a function of tan(beta). Lower mass limits for tan(beta)>1 are set at the 95% confidence level to be m_h > 77.1 GeV and m_A > 77.1 GeV

Search for Extra Dimensions in Boson and Fermion Pair Production in e+e- Interactions at LEP

Extra spatial dimensions are proposed by recent theories that postulate the scale of gravity to be of the same order as the electroweak scale. A sizeable interaction between gravitons and Standard Model particles is then predicted. Effects of these new interactions in boson and fermion pair production are searched for in the data sample collected at centre-of-mass energies above the Z pole by the L3 detector at LEP. In addition, the direct production of a graviton associated with a Z boson is investigated. No statistically significant hints for the existence of these effects are found and lower limits in excess of 1 TeV are derived on the scale of this new theory of gravity

Measurement of Triple-Gauge-Boson Couplings of the W Boson at LEP

We report on measurements of the triple-gauge-boson couplings of the W boson in e+e- collisions with the L3 detector at LEP. W-pair, single-W and single-photon events are analysed in a data sample corresponding to a total luminosity of 76.7 pb^{-1} collected at centre-of-mass energies between 161 GeV and 183 GeV. CP-conserving as well as both C- and P-conserving triple-gauge-boson couplings are determined. The results, in good agreement with the Standard-Model expectations, confirm the existence of the self coupling among the electroweak gauge bosons and constrain its structure

Measurement of Hadron and Lepton-Pair Production at 130GeV < \sqrt{s} < 189 GeV at LEP

We report on measurements of e+e- annihilation into hadrons and lepton pairs. The data have been collected with the L3 detector at LEP at centre-of-mass energies between 130 and 189 GeV. Using a total integrated luminosity of 243.7 pb^-1, 25864 hadronic and 8573 lepton-pair events are selected for the measurement of cross sections and leptonic forward-backward asymmetries. The results are in good agreement with Standard Model predictions