We introduce interpolated multiple Hurwitz polylogs and interpolated multiple Hurwitz zeta values. In addition, we discuss the generating functions for the sum of the polylogs/zeta values of fixed weight, depth, and all heights. The functions are expressed in terms of generalized hypergeometric functions. Compared with the pioneering results of Ohno and Zagier on the generating function, our setup generalizes the results in three directions, namely, at general heights, with a t-interpolation, and as a Hurwitz type. As an application, by fixing the Hurwitz parameter to rational numbers, the generating functions for multiple zeta values with level are given.

In this paper, we establish a vanishing theorem of Nadel type for the Witt multiplier ideals on threefolds over perfect fields of characteristic larger than five. As an application, if a projective normal threefold over $\mathbb{F}_{q}$ is not klt and its canonical divisor is anti-ample, then the number of the rational points on the klt-locus is divisible by $q$.

OBJECTIVES/SPECIFIC AIMS: Unlike the high cure rates (90%) of children with acute lymphoblastic leukemia (ALL), that of adults is still lagging behind and better therapies are needed. Maternal embryonic leucine-zipper kinase (MELK) is aberrantly upregulated in cancer, and implicated in cancer stem cell survival. A recent study has identified FOXM1, a MELK substrate, as a therapeutic target in B cell ALL (B-ALL). Thus, we hypothesized that MELK may act as a therapeutic target in ALL via targeting FOXM1 activity. METHODS/STUDY POPULATION: Western blot and qPCR were used to assess MELK expression in 14 ALL cell lines. Knock-down and kinase inhibition approaches targeting MELK expression and function, followed by CCK-8 and Annexin V (flow cytometry) assays to measure cell viability and apoptosis, respectively. RESULTS/ANTICIPATED RESULTS: MELK was significantly upregulated in patients with ALL (oncomine data analysis). MELK was also significantly higher in B-ALL and T-ALL cell lines compared with that in blood cells of healthy donors. MELK knock-down significantly decreased cell viability (40%–70%, p<0.05, Fig. 1) in ALL cells, and induced apoptosis (~40%). OTS167, a potent MELK inhibitor exhibited cytotoxic activities in both B and T-ALL cells. The IC50 of OTS167 ranged from 20 to 60 nM; we also found a significant increase in apoptosis (p<0.05). Mechanistically, MELK inhibition resulted in decrease of FOXM1 protein levels 3 hours post-treatment. DISCUSSION/SIGNIFICANCE OF IMPACT: MELK is highly expressed in ALL and represents a novel therapeutic target likely via modulating FOXM1 activity. Functional and mechanistic studies will complement and ensure the success of the undergoing Phase I/II clinical trial of OTS167 in patients with refractory or relapsed AML, ALL, and other advanced hematologic malignancies.

4H-SiC substrates were annealed at 1500 °C for 30 min in 0.01 MPa Ar gas flow to make a graphene film. To clarify the effect of Al ion implantation and pre-plasma treatment, the graphene was fabricated on four different kinds of SiC substrates: without plasma treatment, with plasma treatment, Al ion-implanted without plasma treatment and Al ion-implanted with plasma treatment. The graphene films were analyzed by AFM and Raman spectroscopy. The Al ion implanted sample, which was then processed by CF4 plasma, showed small surface roughness of 3.49 nm (RMS), while the sample without CF4 plasma treatment showed large surface roughness of 8.41nm. Similar results were also observed for SiC samples without Al ion implantation. In Raman spectra, strong D-band, G-band and 2D-band signals were detected on both ion-implanted samples after annealing at 1500 °C, but weak D-band were observed on both samples without Al ion implantation. Raman mapping (2D-FWHM) showed that the graphene on ion-implanted SiC treated with CF4 plasma was more homogeneous than the one without CF4 plasma treatment. Hall measurements for SiC without Al ion implantation showed that graphene on SiC treated with CF4 plasma has higher mobility (389 cm2/Vs) than that without plasma treatment (136 cm2/Vs). Additionally, p-type graphene can be fabricated on Al ion-implanted SiC by CF4 plasma treatment.

HoxEr1-xN (x=0.25, 0.5, 0.75) samples were synthesized by nitriding of HoxEr1-x alloy bars and their thermal conductivity κ were measured. The measured κ values were comparable to those of stainless steel and Er3Ni. Ho0.5Er0.5N showed the highest κ of the present three samples. The thermal diffusivity calculated from the κ and the specific heat indicates that Ho0.5Er0.5N is a very promising regenerator material for the cryocoolers. The electrical resistivity ρ was also measured as a function of temperature.

We synthesized ZnS nanocrystals from identical raw material solution by the thermal decomposition of an amine complex. The shapes of products were changed by simply varying heating rate. At higher heating rate, we obtained the isotropic zincblende nanocrystals. At the lower heating rate, the nanorods were formed and the length was increased with the decrease of heating rate. The nanorods had wurtzite structure below 175 °C, and consequently transformed to zincblende phase during a temperature rise to 200 °C. These particle shapes and phases were related to the adsorption properties of amine ligands. Additionally, the synthesized ZnS nanodots and nanorods exhibited predominantly band-edge emission in fluorescence spectra.

A magnetic refrigeration test was performed using a test device filled with spherical GdN material synthesized by the hot isostatic pressing (HIP) method. Refrigeration with an active magnetic regenerator cycle was tested in the temperature range between 48 and 66 K, with the field changing from 1.2 to 3.7 T and 2.0 to 4.0 T at upper and lower sides of the regenerator bed filled with the GdN spheres, respectively. Temperature spans about of 2 K were obtained at both sides, and the total temperature span in each cycle attained about 5 K. The specific heat of the material was measured to calculate the magnetic entropy change ΔS and the adiabatic temperature change ΔT induced by the magnetic field change ΔH. It was suggested that for a given ΔH, larger ΔS and ΔT can be exploited when demagnetized to lower H, especially, to zero field.

We collected charcoal fragments during an archaeological excavation at the Tell Ghanem al-Ali site, located on the lowest terrace of the middle Euphrates River, and measured their radiocarbon ages with accelerator mass spectrometry (AMS). Two trenches, Square-1 and Square-2, were dug on the slope of the tell; 8 building levels were detected in the Square-2 trench. In total, 31 charcoal samples were collected from the 2 trenches, and their calibrated ages ranged from 3100–2900 cal BC at the lowest building level to 2400–2050 cal BC at the uppermost layers of the mound, and concentrated in the period 2650–2450 cal BC. The pottery fragments collected on the surface of the mound before the excavation survey was started, as well as those collected from the sediment layers during the excavation, were assigned on the basis of typological sequences to the Early Bronze Age (EB)-III and EB-IV periods. Thus, the concentrated dates (2650–2450 cal BC) obtained by 14C dating are consistent with the age estimated by archaeological contexts. However, the oldest dates of the lowest level (level-7) go back to 3100–2900 cal BC, and these dates may suggest the existence of the human residence prior to the EB period at the site, and may therefore lead to a revision of the oldest age limit of the EB period currently accepted in the region.

Whole-genome scans have identified Dmo1 as a major quantitative trait locus (QTL) for obesity and dyslipidaemia in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. We have produced congenic rats for the Dmo1 locus, using marker-assisted speed congenic protocols, enforced by selective removal of other QTL regions (QTL-marker-assisted counterselection), to efficiently transfer chromosomal segments from non-diabetic Fischer 344 (F344) rats into the OLETF background. In the third generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. We conclude that single-allele correction of an impaired genetic pathway can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.