Some mixed Hodge structure on l^2-cohomology of covering of K\"ahler manifolds

We give methods to compute l^2-cohomology groups of a covering manifolds obtained by removing pullback of a (normal crossing) divisor to a covering of a compact K\"ahler manifold. We prove that in suitable quotient categories, these groups admit natural mixed Hodge structure whose graded pieces are given by expected Gysin maps.Comment: 40 pages. This revised version will be published in Mathematische Annale

Early-time free-surface flow driven by a deforming boundary

AbstractWhen a solid boundary deforms rapidly into a quiescent liquid layer, a flow is induced that can lead to jet formation. An asymptotic analytical solution is presented for this flow, driven by a solid boundary deforming with dimensionless vertical velocity $V_{b}(x,t)={\it\epsilon}(1+\cos x)\,f(t)$, where the amplitude ${\it\epsilon}$ is small relative to the wavelength and the time dependence $f(t)$ approaches 0 for large $t$. Initially, the flow is directed outwards from the crest of the deformation and slows with the slowing of the boundary motion. A domain-perturbation method is used to reveal that, when the boundary stops moving, nonlinear interactions with the free surface leave a remnant momentum directed back towards the crest, and this momentum can be a precursor to jet formation. This scenario arises in a laser-induced printing technique in which an expanding blister imparts momentum into a liquid film to form a jet. The analysis provides insight into the physics underlying the interaction between the deforming boundary and free surface, in particular, the dependence of the remnant flow on the thickness of the liquid layer and the deformation amplitude and wavelength. Numerical simulations are used to show the range of validity of the analytical results, and the domain-perturbation solution is extended to an axisymmetric domain with a Gaussian boundary deformation to compare with previous numerical simulations of blister-actuated laser-induced forward transfer.The authors gratefully acknowledge financial support for this research from the Na- tional Science Foundation MRSEC program through the Princeton Center for Complex Materials (grant DMR-0819860).This is the accepted manuscript. The final published version is available from CUP at http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=9571518&fileId=S0022112015000749

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

2-Cyanobenzothiazoles (CBTs) are useful building blocks for: 1) luciferin derivatives for bioluminescent imaging; and 2) handles for bioorthogonal ligations. A particularly versatile CBT is 6-amino-2-cyanobenzothiazole (ACBT), which has an amine handle for straight-forward derivatisation. Here we present an economical and scalable synthesis of ACBT based on a cyanation catalysed by 1,4-diazabicyclo[2.2.2]octane (DABCO), and discuss its advantages for scale-up over previously reported routes

Behavioral implications of shortlisting procedures

We consider two-stage “shortlisting procedures” in which the menu of alternatives is first pruned by some process or criterion and then a binary relation is maximized. Given a particular first-stage process, our main result supplies a necessary and sufficient condition for choice data to be consistent with a procedure in the designated class. This result applies to any class of procedures with a certain lattice structure, including the cases of “consideration filters,” “satisficing with salience effects,” and “rational shortlist methods.” The theory avoids background assumptions made for mathematical convenience; in this and other respects following Richter’s classical analysis of preference-maximizing choice in the absence of shortlisting

Effects of local hypothermia-rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord.

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI

Neutrino-driven Explosions

The question why and how core-collapse supernovae (SNe) explode is one of the central and most long-standing riddles of stellar astrophysics. A solution is crucial for deciphering the SN phenomenon, for predicting observable signals such as light curves and spectra, nucleosynthesis, neutrinos, and gravitational waves, for defining the role of SNe in the evolution of galaxies, and for explaining the birth conditions and properties of neutron stars (NSs) and stellar-mass black holes. Since the formation of such compact remnants releases over hundred times more energy in neutrinos than the SN in the explosion, neutrinos can be the decisive agents for powering the SN outburst. According to the standard paradigm of the neutrino-driven mechanism, the energy transfer by the intense neutrino flux to the medium behind the stagnating core-bounce shock, assisted by violent hydrodynamic mass motions (sometimes subsumed by the term "turbulence"), revives the outward shock motion and thus initiates the SN blast. Because of the weak coupling of neutrinos in the region of this energy deposition, detailed, multidimensional hydrodynamic models including neutrino transport and a wide variety of physics are needed to assess the viability of the mechanism. Owing to advanced numerical codes and increasing supercomputer power, considerable progress has been achieved in our understanding of the physical processes that have to act in concert for the success of neutrino-driven explosions. First studies begin to reveal observational implications and avenues to test the theoretical picture by data from individual SNe and SN remnants but also from population-integrated observables. While models will be further refined, a real breakthrough is expected through the next Galactic core-collapse SN, when neutrinos and gravitational waves can be used to probe the conditions deep inside the dying star. (abridged)Comment: Author version of chapter for 'Handbook of Supernovae,' edited by A. Alsabti and P. Murdin, Springer. 54 pages, 13 figure

Riociguat: Mode of action and clinical development in pulmonary hypertension

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure and increased pulmonary vascular resistance. If untreated, they can result in death due to right heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. Here we describe in detail the role of the nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH, and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and the pivotal Phase III randomized clinical trials in PAH and CTEPH

Population-level effect of HSV-2 therapy on the incidence of HIV in sub-Saharan Africa.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown. METHODS: The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness. RESULTS: Clinician-initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%. CONCLUSIONS: These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour