This paper presents the use of nanoscale chemistry to synthesize a multilevel, hierarchically built nanoparticle, which we define as a nanoclinic, for targeted diagnostics and therapy. This nanoclinic, produced by multistep chemistry in a nanosize micelle, consists of a thin silica shell encapsulating magnetic (Fe2O3) nanoparticles and fluorescent dyes for enhanced contrast magnetic resonance and optical imaging and magnetic-induced cancer therapy. Furthermore, the surface of these prototype nanoclinics is functionalized with a biotargeting group, luteinizing hormone-releasing hormone (LH−RH). In the work reported here, the LH−RH targets receptor-specific cancer cells for utilization in imaging and investigation of biological effects. The structure and function of these nanoclinics have been characterized using electron and X-ray diffractions, transmission electron microscopy, atomic force and scanning electron microscopy and two-photon laser scanning microscopy. Targeting of the receptor-specific cells has been demonstrated, along with the demonstration of a new mechanism of selective destruction of cancer cells, in a dc magnetic field, using these magnetic nanoclinics.

The entire nucleotide sequence of cloned cDNAs containing the 5'-untranslated region and gene 1 of Purdue-115 strain of transmissible gastroenteritis virus (TGEV) was determined. This completes the sequence of the TGEV genome, which is 28,579 nucleotides long. The gene 1 is composed of two large open reading frames, ORF1a and ORF1b, which contain 4017 and 2698 codons, respectively (stop excluded). A brief, three-codon-long ORF is present upstream of ORF1a. ORF1b overlaps ORF1a by 43 bases in the (-1) reading frame. In vitro experiments indicated that translation of the ORF1a/b polyprotein involves an efficient ribosomal frameshifting activity, as previously shown for other coronaviruses. Analysis of the predicted ORF1a and ORF1b translation products revealed that the putative functional domains identified in infectious bronchitis virus (IBV), mouse hepatitis virus (MHV) and human coronavirus 229E (HCV 229E) are all present in TGEV. The amino-terminal half of the ORF1a product exhibits greater divergence than the carboxyl-terminal half, including within the TGEV/HCV229E pair. The ORF1b protein is overall highly conserved among the above four coronaviruses, except a divergent region situated near the carboxy terminus.

We have measured the ac nonlinear susceptibilities ^3, ^5, and Xi of very dilute Ag:Mn spin-glasses above and below^ the transition temperature Tg as functions of frequency, temperature, and magnetic field. In the static limit, these quantities display well defined critical singularities at Tg. The nonlinear susceptibilities can be fitted above Tg by powers of frequency with weakly temperature-dependent exponents. While the effective exponents satisfy the relations imposed by static and dynamic scaling, the observed temperature and frequency roundings suggest the presence of additional length scales. PACS numbers: 75.30.Cr, 64.60.-i, 75.30.Hx, 75.30.KzMetallic spin-glasses consist of magnetic impurities diluted in a noble metal (e.g., Mn, S = f in Ag). As a result of their positional disorder, their exchange interaction / which is mediated by the conduction electrons is random. Impurities separated by distances /? < 35 A interact more strongly through the preasymptotic corrections^ to the Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction -COS(2^F^)/^^-In addition to the exchange forces, the spin-orbit scattering of the conduction electrons by impurities gives rise to a random anisotropy D (Dzyaloshinsky-Moriya), measured to be -9x10"^ times smaller than the exchange.^ The dependence of the susceptibility of these alloys with temperature exhibits a sharp cusp [ Fig. 1(b)], which may be associated either with a gradual freezing of the spins or a genuine phase transition. The existence of a true singularity in the free energy at the spin-glass transition temperature Tg should be manifest in the power-law divergence of all nonlinear magnetic susceptibilities,^ and their observations should be considered as convincing experimental evidence of a phase transition."*'^ Dynamical studies have been limited so far to the linear susceptibility. ^ We report for the first time a complete spectroscopic study of the nonlinear susceptibilities at ultra-low frequencies (from 10"^ to 10 Hz) above and below the transition.In the vicinity of Tg, the nonlinearities are easily detected in the magnetization response M(0,0 ^^X^^it xcos(A; ftf )"f^itsin(/cOO} to a harmonic magnetic field hcosiO^t)[ Fig. 2(a)]. The nonlinear susceptibilities Xin^x parametrize the expansion of M in odd powers (by virtue of time-reversal invariance) of A. ^ In general, each amplitude Bk contains contributions from all sucep-0.092

In a magnetic field, spin-ladders undergo two zero-temperature phase transitions at the critical fields Hc1 and Hc2. An experimental review of static and dynamical properties of spin-ladders close to these critical points is presented. The scaling functions, universal to all quantum critical points in onedimension, are extracted from (a) the thermodynamic quantities (magnetization) and (b) the dynamical functions (NMR relaxation). A simple mapping of strongly coupled spin ladders in a magnetic field on the exactly solvable XXZ model enables to make detailed fits and gives an overall understanding of a broad class of quantum magnets in their gapless phase (between Hc1 and Hc2). In this phase, the low temperature divergence of the NMR relaxation demonstrates its Luttinger liquid nature as well as the novel quantum critical regime at higher temperature. The general behavior close these quantum critical points can be tied to known models of quantum magnetism.PACS. 75.10.Jm Quantized spin models -75.40.-s Critical-points effects, specific heats, short range order -76.60.-k Nuclear magnetic resonance and relaxation

This phase I study aimed to determine the recommended dose (RD), safety profile, and feasibility of a procedure combining intratumoral injection of hafnium oxide nanoparticles (NBTXR3; a radioenhancer) and external beam radiotherapy (EBRT) for preoperative treatment of adults with locally advanced soft tissue sarcoma (STS). Patients had a preoperative indication of EBRT for STS of the extremity or trunk. Baseline tumor volume (TV) was calculated by MRI. NBTXR3 was injected percutaneously into tumors at 53.3 g/L. Dose escalation was based on four levels equivalent to 2.5%, 5%, 10%, and 20% of baseline TV. NBTXR3 was visualized in the tumor 24 hours postinjection, and EBRT was initiated (50 Gy over 5 weeks). Surgery was performed 6 to 8 weeks after EBRT completion. Twenty-two patients completed NBTXR3 injection, EBRT, and surgery and were followed for a median 22 months (range, 6-40). At NBTXR3 20% of TV, two dose-limiting toxicities occurred: injection-site pain and postoperative scar necrosis. The RD was defined as 10%. No leakage of NBTXR3 into surrounding tissues occurred; intratumor NBTXR3 levels were maintained during radiotherapy. At the RD, median tumor shrinkage was 40% (range 71% shrinkage, 22% increase); median percentage of residual viable tumor cells was 26% (range, 10%-90%). Patients receiving 20% of TV demonstrated pathologic complete responses. Seven grade 3 adverse events occurred, which were reversible. A single intratumoral injection of NBTXR3 at 10% of TV with preoperative EBRT was technically feasible with manageable toxicity; clinical activity was observed. .