The biological and clinical behaviors of hematological malignancies can be influenced by the active crosstalk with an altered bone marrow (BM) microenvironment. In the present study, we provide a detailed picture of the BM vasculature in acute myeloid leukemia using intravital two-photon microscopy. We found several abnormalities in the vascular architecture and function in patient-derived xenografts (PDX), such as vascular leakiness and increased hypoxia. Transcriptomic analysis in endothelial cells identified nitric oxide (NO) as major mediator of this phenotype in PDX and in patient-derived biopsies. Moreover, induction chemotherapy failing to restore normal vasculature was associated with a poor prognosis. Inhibition of NO production reduced vascular permeability, preserved normal hematopoietic stem cell function, and improved treatment response in PDX.

We present the cross sections for production of up to four jets at the Large Hadron Collider, at next-to-leading order in the QCD coupling. We use the BlackHat library in conjunction with SHERPA and a recently developed algorithm for assembling primitive amplitudes into color-dressed amplitudes. We adopt the cuts used by ATLAS in their study of multijet events in $pp$ collisions at $\sqrt{s}=7\mathrm{TeV}$. We include estimates of nonperturbative corrections and compare to ATLAS data. We store intermediate results in a framework that allows the inexpensive computation of additional results for different choices of scale or parton distributions.

The production of $W$ bosons in association with jets is an important background to new physics at the LHC. Events in which the $W$ carries large transverse momentum and decays leptonically lead to large missing energy and are of particular importance. We show that the left-handed nature of the $W$ coupling, combined with valence quark domination at a $pp$ machine, leads to a large left-handed polarization for both $W^{+}$ and $W^{-}$ bosons at large transverse momenta. The polarization fractions are very stable with respect to QCD corrections. The leptonic decay of the $W^{\pm }$ bosons translates the common left-handed polarization into a strong asymmetry in transverse momentum distributions between positrons and electrons and between neutrinos and antineutrinos (missing transverse energy). Such asymmetries may provide an effective experimental handle on separating $W+\mathrm{\text{jets}}$ from top-quark production, which exhibits very little asymmetry due to C invariance, and from various types of new physics.

We address the issue of minimizing the heat generated when erasing the information stored in an array of quantum dots in finite time. We identify the fundamental limitations and trade-offs involved in this process and analyze how a feedback operation can help improve it.

The cerebral cortex contains multiple areas with distinctive cytoarchitectonic patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have investigated the neuronal output of individual progenitor cells in the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. Our experimental results indicate that progenitor cells generate pyramidal cell lineages with a wide range of sizes and laminar configurations. Mathematical modeling indicates that these outcomes are compatible with a stochastic model of cortical neurogenesis in which progenitor cells undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Our findings support a mechanism for cortical neurogenesis whose flexibility would make it capable to generate the diverse cytoarchitectures that characterize distinct neocortical areas.

The mechanism whereby the morphology and connectivity of the dendritic tree is regulated depends on an actin dynamics that, in turn, is controlled by Rho GTPases, a family of small GTP-binding proteins encompassing Rho, Rac, and Cdc42 subfamilies. Cytotoxic necrotizing factor 1 (CNF1), a protein toxin from Escherichia coli , constitutively activates Rho GTPases, thus leading to remodeling of the actin cytoskeleton in intact cells. Here, we show that the modulation of cerebral RhoA and Rac1 activity induced by CNF1 in mice leads to ( i ) rearrangement of cerebral actin cytoskeleton, ( ii ) enhanced neurotransmission and synaptic plasticity, and ( iii ) improved learning and memory in various behavioral tasks. The effects persist for weeks and are not observed in mice treated with a recombinant CNF1, in which the enzymatic activity was abolished by substituting serine to cysteine at position 866. The results suggest that learning ability can be improved through pharmacological manipulation of neural connectivity.