Position-Selected Molecular Ruler

The molecular ruler method allows the precise control of the gap between a parent gold structure and a deposited daughter structure using a conveniently grown self-assembled molecular multilayer as a lithographic mask. However, we cannot choose a position where the gap should be placed, since the ruler attaches to all exposed gold surfaces. In this work, a convenient method of selecting the position of nanogaps by further patterning the molecular multilayer using low-energy electron beam irradiation and piranha etchant is described

Exploiting Don\u27t Cares to Enhance Functional Tests

In simulation based design verification, deterministic or pseudo-random tests are used to check functional correctness of a design. In this paper we present a technique generating tests by specifying the don’t care inputs in the functional specifications so as to improve their coverage of both design errors and manufacturing faults. The don’t cares are chosen to maximize sensitization of signals in the circuit. The tests generated in this way require only a fraction of pseudo-exhaustive test patterns to achieve a high multiplicity of fault coverage

No atypical white-matter structures in grapheme- or color-sensitive areas in synesthetes

Grapheme-color synesthetes experience colors when presented with written language characters. In this study diffusion-weighted imaging was used to investigate white matter alterations in color-and grapheme-processing brain areas in synesthetes as a possible factor for the color sensations. Regions of interest were defined by means of neuroanatomical atlantes, functional localizer tasks and retinotopic mapping. None of the regions showed differences in white matter structure between synesthetes and a control population, as revealed by fractional anisotropy and mean diffusivity measures. Quite the contrary, the data broadly supported the null hypothesis of no group differences in white matter microstructure. This finding is in line with recent studies suggesting no atypical neuroanatomy in grapheme-color synesthetes.

Should Aggressive Surgical Local Control Be Attempted in All Patients with Metastatic or Pelvic Ewing's Sarcoma?

In previous reports, patients with Ewing's sarcoma received radiation therapy (XRT) for definitive local control because metastatic disease and pelvic location were thought to preclude aggressive local treatment. We sought to determine if single-site metastatic disease should be treated differently from multicentric-metastatic disease. We also wanted to reinvestigate the impact of XRT, pelvic location, and local recurrence on outcomes. Our results demonstrated a significant difference in overall survival (OS) between patients with either localized disease or a single-metastatic site and patients with multicentric-metastatic disease (P = 0.004). Local control was also found to be an independent predictor of outcomes as demonstrated by a significant difference in OS between those with and without local recurrence (P = 0.001). Axial and pelvic location did not predict a decreased OS. Based on these results, we concluded that pelvic location and the diagnosis of metastatic disease at diagnosis should not preclude aggressive local control, except in cases of multicentric-metastatic disease

Real-world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres.

The clinical course of chronic lymphocytic leukaemia (CLL) is heterogeneous, and treatment options vary considerably. The Connect® CLL registry is a multicentre, prospective observational cohort study that provides a real-world perspective on the management of, and outcomes for, patients with CLL. Between 2010 and 2014, 1494 patients with CLL and that initiated therapy, were enrolled from 199 centres throughout the USA (179 community-, 17 academic-, and 3 government-based centres). Patients were grouped by line of therapy at enrolment (LOT). We describe the clinical and demographic characteristics of, and practice patterns for, patients with CLL enrolled in this treatment registry, providing patient-level observational data that represent real-world experiences in the USA. Fluorescence in situ hybridization (FISH) analyses were performed on 49·3% of patients at enrolment. The most common genetic abnormalities detected by FISH were del(13q) and trisomy 12 (45·7% and 20·8%, respectively). Differences in disease characteristics and comorbidities were observed between patients enrolled in LOT1 and combined LOT2/≥3 cohorts. Important trends observed include the infrequent use of genetic prognostic testing, and differences in patient characteristics for patients receiving chemoimmunotherapy combinations. These data represent experiences of patients with CLL in the USA, which may inform treatment decisions in everyday practice

Bradyzoite pseudokinase 1 is crucial for efficient oral infectivity of the Toxoplasma gondii tissue cyst.

The tissue cyst formed by the bradyzoite stage of Toxoplasma gondii is essential for persistent infection of the host and oral transmission. Bradyzoite pseudokinase 1 (BPK1) is a component of the cyst wall, but nothing has previously been known about its function. Here, we show that immunoprecipitation of BPK1 from in vitro bradyzoite cultures, 4 days postinfection, identifies at least four associating proteins: MAG1, MCP4, GRA8, and GRA9. To determine the role of BPK1, a strain of Toxoplasma was generated with the bpk1 locus deleted. This BPK1 knockout strain (Δbpk1) was investigated in vitro and in vivo. No defect was found in terms of in vitro cyst formation and no difference in pathogenesis or cyst burden 4 weeks postinfection (wpi) was detected after intraperitoneal (i.p.) infection with Δbpk1 tachyzoites, although the Δbpk1 cysts were significantly smaller than parental or BPK1-complemented strains at 8 wpi. Pepsin-acid treatment of 4 wpi in vivo cysts revealed that Δbpk1 parasites are significantly more sensitive to this treatment than the parental and complemented strains. Consistent with this, 4 wpi Δbpk1 cysts showed reduced ability to cause oral infection compared to the parental and complemented strains. Together, these data reveal that BPK1 plays a crucial role in the in vivo development and infectivity of Toxoplasma cysts