A B S T R A C T The concentration of multiplication stimulating activity (MSA), an insulinlike growth factor (IGF), is high in fetal rat serum. We now report that MSA is exclusively associated wth an albumin-size binding protein in fetal rat serum; the growth hormone-dependent, gamma globulin-size binding protein, which predominates in the older animal, is absent from fetal rat serum. When 125I-MSA was incubated with fetal rat serum and then gel filtered on Sephadex G-200, specific radioactivity eluted in the void volume (peak I) and the albumin region (peak III); by contrast, specific radioactivity eluted mainly in the gamma globulin region (peak II)

We present measurements of the branching fraction and time-dependent CP asymmetries in B0-->J/psipi0 decays based on 466 x 10(6) Upsilon(4S)-->BB over events collected with the BABAR detector at the SLAC PEP-II asymmetric-energy B factory. We measure the CP asymmetry parameters S= -1.23+/-0.21(stat)+/-0.04(syst) and C= -0.20+/-0.19(stat)+/-0.03(syst), where the measured value of (S, C) is 4.0 standard deviations from (0, 0) including systematic uncertainties. The branching fraction is determined to be B(B0-->J/psipi0)=[1.69+/-0.14(stat)+/-0.07(syst)]x10(-5).

Transcriptional profiling has revealed a diverse range of cancer cell states, however an understanding of their function has remained elusive. Using a combination of zebrafish melanoma modeling and human validation, we have identified a conserved stress-like state that confers intrinsic drug resistance. The stress-like state expresses genes such as fos , hsp70 and ubb , all required for adaptation to diverse cellular stresses, and we confirmed its existence using immunofluorescence and spatial transcriptomics. We provide evidence that this state has a higher tumor seeding capabilities compared to non-stressed cells, and confers intrinsic resistance to MEK inhibitors, a commonly used melanoma therapeutic. Furthermore, the stress-like program can be induced by extrinsic processes such as heat shock, and confers resistance to both MEK and BRAF inhibitors in both zebrafish and human melanomas.Collectively, our study suggests that the transcriptional states associated with therapeutic failure are established during the earliest steps of tumorigenesis.

A study of the structural and magnetic properties of sequentially deposited (multilayered) sputtered films of Gd and Co is presented. It is found that by varying the deposition temperature, the film composition, and the multilayer sequences the film morphology can'be controlled in a continuous way and, thus, new magnetic structures achieved. In particular, samples deposited at ambient temperature (80'C) show clear evidence of layering and have fairly simple magnetic properties. On the other hand, at elevated deposition temperature (380'C) no evidence of layers is seen, but one finds a pronounced chemical reaction which results in the formation of GdCo2 in all cases where the nominal composition is on the Co-rich side of GdCo2. It is demonstrated that one can take advantage of this reaction and use the multilayer sequences to control extrinsic properties of the films such as coercivity.

SummaryOncogenic alterations to DNA are not transforming in all cellular contexts1,2. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype has a unique tropism for the limbs, specifically the hands and feet3. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.