163 research outputs found
KDE Based Coarse-graining of Semicrystalline Systems with Correlated Three-body Intramolecular Interaction
We present an extension to the iterative Boltzmann inversion method to
generate coarse-grained models with three-body intramolecular potentials that
can reproduce correlations in structural distribution functions. The
coarse-grained structural distribution functions are computed using kernel
density estimates to produce analytically differentiable distribution functions
with controllable smoothening via the kernel bandwidth parameters. Bicubic
interpolation is used to accurately interpolate the three-body potentials
trained by the method. To demonstrate this new approach, a coarse-grained model
of polyethylene is constructed in which each bead represents an ethylene
monomer. The resulting model reproduces the radial density function as well as
the joint probability distribution of bond-length and bond-angles sampled from
target atomistic simulations with only a 10% increase in the computational cost
compared to models with independent bond-length and bond-angle potentials.
Analysis of the predicted crystallization kinetics of the model developed by
the new approach reveals that the bandwidth parameters can be tuned to
accelerate the modeling of polymer crystallization. Specifically, computing
target RDF with larger bandwidth slows down the secondary crystallization, and
increasing the bandwidth in -direction of bond-length and bond-angle
distribution reduces the primary crystallization rate.Comment: To be submitted; 31 pages; 8 figure
Ang II (Angiotensin II) Conversion to Angiotensin-(1-7) in the Circulation Is POP (Prolyloligopeptidase)-Dependent and ACE2 (Angiotensin-Converting Enzyme 2)-Independent
The Ang II (Angiotensin II)-Angiotensin-(1-7) axis of the Renin Angiotensin System encompasses 3 enzymes that form Angiotensin-(1-7) [Ang-(1-7)] directly from Ang II: ACE2 (angiotensin-converting enzyme 2), PRCP (prolylcarboxypeptidase), and POP (prolyloligopeptidase). We investigated their relative contribution to Ang-(1-7) formation in vivo and also ex vivo in serum, lungs, and kidneys using models of genetic ablation coupled with pharmacological inhibitors. In wild-type (WT) mice, infusion of Ang II resulted in a rapid increase of plasma Ang-(1-7). In ACE2−/−/PRCP−/− mice, Ang II infusion resulted in a similar increase in Ang-(1-7) as in WT (563±48 versus 537±70 fmol/mL, respectively), showing that the bulk of Ang-(1-7) formation in circulation is essentially independent of ACE2 and PRCP. By contrast, a POP inhibitor, Z-Pro-Prolinal reduced the rise in plasma Ang-(1-7) after infusing Ang II to control WT mice. In POP−/− mice, the increase in Ang-(1-7) was also blunted as compared with WT mice (309±46 and 472±28 fmol/mL, respectively P=0.01), and moreover, the rate of recovery from acute Ang II-induced hypertension was delayed (P=0.016). In ex vivo studies, POP inhibition with ZZP reduced Ang-(1-7) formation from Ang II markedly in serum and in lung lysates. By contrast, in kidney lysates, the absence of ACE2, but not POP, obliterated Ang-(1-7) formation from added Ang II. We conclude that POP is the main enzyme responsible for Ang II conversion to Ang-(1-7) in the circulation and in the lungs, whereas Ang-(1-7) formation in the kidney is mainly ACE2-dependent.Peer reviewe
Optical dual-comb Vernier division of an octave-spanning Kerr microcomb
We measure the repetition rate of a 900 GHz octave-spanning soliton microcomb based on Vernier dual-comb frequency division implemented with two silicon nitride microresonator combs fabricated on the same wafer
Top-gated graphene field-effect-transistors formed by decomposition of SiC
Top-gated, few-layer graphene field-effect transistors (FETs) fabricated on
thermally-decomposed semi-insulating 4H-SiC substrates are demonstrated.
Physical vapor deposited SiO2 is used as the gate dielectric. A two-dimensional
hexagonal arrangement of carbon atoms with the correct lattice vectors,
observed by high-resolution scanning tunneling microscopy, confirms the
formation of multiple graphene layers on top of the SiC substrates. The
observation of n-type and p-type transition further verifies Dirac Fermions
unique transport properties in graphene layers. The measured electron and hole
mobility on these fabricated graphene FETs are as high as 5400 cm2/Vs and 4400
cm2/Vs respectively, which are much larger than the corresponding values from
conventional SiC or silicon
Urinary renin in patients and mice with diabetic kidney disease
In patients with diabetic kidney disease (DKD), plasma renin activity is usually decreased, but there is limited information on urinary renin and its origin. Urinary renin was evaluated in samples from patients with longstanding type I diabetes mellitus and mice with streptozotocin-induced diabetes mellitus. Renin-reporter mouse model (Ren1d-Cre;mT/ mG) was made diabetic with streptozotocin to examine whether the distribution of cells of the renin lineage was altered in a chronic diabetic environment. Active renin was increased in urine samples from patients with DKD (n=36), compared with those without DKD (n=38; 3.2 versus 1.3 pg/mg creatinine; P<0.001). In mice with streptozotocin-induced diabetes mellitus, urine renin was also increased compared with nondiabetic controls. By immunohistochemistry, in mice with streptozotocin-induced diabetes mellitus, juxtaglomerular apparatus and proximal tubular renin staining were reduced, whereas collecting tubule staining, by contrast, was increased. To examine the role of filtration and tubular reabsorption on urinary renin, mice were either infused with either mouse or human recombinant renin and lysine (a blocker of proximal tubular protein reabsorption). Infusion of either form of renin together with lysine markedly increased urinary renin such that it was no longer different between nondiabetic and diabetic mice. Megalin mRNA was reduced in the kidney cortex of streptozotocin-treated mice (0.70±0.09 versus 1.01±0.04 in controls, P=0.01) consistent with impaired tubular reabsorption. In Ren1d-Cre;mT/mG with streptozotocin-induced diabetes mellitus, the distribution of renin lineage cells within the kidney was similar to nondiabetic renin-reporter mice. No evidence for migration of cells of renin linage to the collecting duct in diabetic mice could be found. Renin mRNA in microdissected collecting ducts from streptozotocin-treated mice, moreover, was not significantly different than in controls, whereas in kidney cortex, largely reflecting juxtaglomerular apparatus renin, it was significantly reduced. In conclusion, in urine from patients with type 1 diabetes mellitus and DKD and from mice with streptozotocin-induced diabetes mellitus, renin is elevated. This cannot be attributed to production from cells of the renin lineage migrating to the collecting duct in a chronic hyperglycemic environment. Rather, the elevated levels of urinary renin found in DKD are best attributed to altered glomerular filteration and impaired proximal tubular reabsorption.Fil: Tang, Jeannette. Northwestern University; Estados UnidosFil: Wysocki, Jan. Northwestern University; Estados UnidosFil: Ye, Minghao. Northwestern University; Estados UnidosFil: Garramuño, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Centro CientÃfico Tecnológico Conicet - Mendoza. Instituto de Medicina y BiologÃa Experimental de Cuyo; ArgentinaFil: Rein, Johannes. Northwestern University; Estados UnidosFil: Shirazi, Mina. Northwestern University; Estados UnidosFil: Bader, Michael. Charité Universitätsmedizin; AlemaniaFil: Gomez, Roberto Ariel. University of Virginia; Estados UnidosFil: Sequeira Lopez, Maria Luisa S.. University of Virginia; Estados UnidosFil: Afkarian, Maryam. University of California at Davis; Estados UnidosFil: Batlle, Daniel. Northwestern University; Estados Unido
Optical Division of an Octave-Spanning Comb on an All-Silicon Nitride Platform
We demonstrate optical frequency division of an octave-spanning large repetition rate microcomb to an electronically-detectable frequency in an all-silicon nitride dual microcomb platform
Vernier Microcombs for Integrated Optical Atomic Clocks
CMOS-compatible Kerr microcombs have drawn substantial interest as
mass-manufacturable, compact alternatives to bulk frequency combs. This could
enable deployment of many comb-reliant applications previously confined to
laboratories. Particularly enticing is the prospect of microcombs performing
optical frequency division in compact optical atomic clocks. Unfortunately, it
is difficult to meet the self-referencing requirement of microcombs in these
systems due to the THz repetition rates typically required for
octave-spanning comb generation. Additionally, it is challenging to spectrally
engineer a microcomb system to align a comb mode with an atomic clock
transition with sufficient signal-to-noise ratio. Here, we adopt a Vernier
dual-microcomb scheme for optical frequency division of a stabilized
ultranarrow-linewidth continuous-wave laser at 871 nm to a 235 MHz output
frequency. In addition to enabling measurement of the comb repetition rates,
this scheme brings the freedom to pick comb lines from either or both of the
combs. We exploit this flexibility to shift an ultra-high-frequency (100
GHz) carrier-envelope offset beat down to frequencies where detection is
possible and to place a comb line close to the 871 nm laser - tuned so that if
frequency-doubled it would fall close to the clock transition in
Yb. Moreover, we introduce a novel scheme which suppresses
frequency noise arising from interferometric phase fluctuations in our
dual-comb system and reduces the frequency instability down to our measurement
limit. Our dual-comb system can potentially combine with an integrated ion trap
toward future chip-scale optical atomic clocks
LIS1 Regulates Osteoclast Formation and Function through Its Interactions with Dynein/Dynactin and Plekhm1
Microtubule organization and lysosomal secretion are both critical for the activation and function of osteoclasts, highly specialized polykaryons that are responsible for bone resorption and skeletal homeostasis. Here, we have identified a novel interaction between microtubule regulator LIS1 and Plekhm1, a lysosome-associated protein implicated in osteoclast secretion. Decreasing LIS1 expression by shRNA dramatically attenuated osteoclast formation and function, as shown by a decreased number of mature osteoclasts differentiated from bone marrow macrophages, diminished resorption pits formation, and reduced level of CTx-I, a bone resorption marker. The ablated osteoclast formation in LIS1-depleted macrophages was associated with a significant decrease in macrophage proliferation, osteoclast survival and differentiation, which were caused by reduced activation of ERK and AKT by M-CSF, prolonged RANKL-induced JNK activation and declined expression of NFAT-c1, a master transcription factor of osteoclast differentiation. Consistent with its critical role in microtubule organization and dynein function in other cell types, we found that LIS1 binds to and colocalizes with dynein in osteoclasts. Loss of LIS1 led to disorganized microtubules and aberrant dynein function. More importantly, the depletion of LIS1 in osteoclasts inhibited the secretion of Cathepsin K, a crucial lysosomal hydrolase for bone degradation, and reduced the motility of osteoclast precursors. These results indicate that LIS1 is a previously unrecognized regulator of osteoclast formation, microtubule organization, and lysosomal secretion by virtue of its ability to modulate dynein function and Plekhm1
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