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We derive Galactic continuum spectra from 5-96 cm −1 from COBE/FIRAS observations. The spectra are dominated by warm dust emission, which may be fit with a single temperature in the range 16-21 K (for ν 2 emissivity) along each line of sight. Dust heated by the attenuated radiation field in molecular clouds gives rise to intermediate temperature (10-14 K) emission in the inner Galaxy only. A widespread, very cold component (4-7 K) with optical depth that is spatially correlated with the warm component is also detected. The cold component is unlikely to be due to very cold dust shielded from starlight, because it is present at high latitude. We consider hypotheses that the cold component is due to enhanced submillimeter emissivity of the dust that gives rise to the warm component, or that it may be due to very small, large, or fractal particles. Lack of substantial power above the emission from warm dust places 1 The National Aeronautics and Space Administration/ Goddard Space Flight Center (NASA/GSFC) is responsible for the design, development, and operation of the Cosmic Background Explorer (COBE). Scientific guidance is provided by the COBE Science Working Group. GSFC is also responsible for the development of the analysis software and for the production of the mission data sets.-2strong constraints on the amount of cold gas in the Galaxy. The microwave sky brightness due to interstellar dust is dominated by the cold component, and its angular variation could limit our ability to discern primordial fluctuations in the cosmic microwave background radiation.

Purpose AZD1775 is a WEE1 kinase inhibitor targeting G2 checkpoint control, preferentially sensitizing TP53-deficient tumor cells to DNA damage. This phase I study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of oral AZD1775 as monotherapy or in combination with chemotherapy in patients with refractory solid tumors. Patients and Methods In part 1, patients received a single dose of AZD1775 followed by 14 days of observation. In part 2, patients received AZD1775 as a single dose (part 2A) or as five twice per day doses or two once per day doses (part 2B) in combination with one of the following chemotherapy agents: gemcitabine (1,000 mg/m), cisplatin (75 mg/m), or carboplatin (area under the curve, 5 mg/mL⋅min). Skin biopsies were collected for pharmacodynamic assessments. TP53 status was determined retrospectively in archival tumor tissue. Results Two hundred two patients were enrolled onto the study, including nine patients in part 1, 43 in part 2A (including eight rollover patients from part 1), and 158 in part 2B. AZD1775 monotherapy given as single dose was well tolerated, and the maximum-tolerated dose was not reached. In the combination regimens, the most common adverse events consisted of fatigue, nausea and vomiting, diarrhea, and hematologic toxicity. The maximum-tolerated doses and biologically effective doses were established for each combination. Target engagement, as a predefined 50% pCDK1 reduction in surrogate tissue, was observed in combination with cisplatin and carboplatin. Of 176 patients evaluable for efficacy, 94 (53%) had stable disease as best response, and 17 (10%) achieved a partial response. The response rate in TP53-mutated patients (n = 19) was 21% compared with 12% in TP53 wild-type patients (n = 33). Conclusion AZD1775 was safe and tolerable as a single agent and in combination with chemotherapy at doses associated with target engagement.

Articles you may be interested inDynamic and dielectric response of charged colloids in electrolyte solutions to external electric fields Sound speed dispersion measurements and their interpretation in the presence of a shallow buried layer.The standard description of electrokinetic phenomena deals with a particle whose charge is uniformly smeared over its surface and considers ion transport only within a Gouy-Chapman diffuse layer. Experimental studies with colloidal dispersions have shown that this model is not applicable to many systems. To encompass a wider class of behavior, the standard model was extended to include ion migration within the Stern layer, the region between the shear envelope and the rigid particle. Computations show that Stern layer transport increases the conductivity and dielectric response of suspensions as well as the magnitude of the {; potential inferred from mobility measurements. Model predictions are compared with experimental measurements on two well-defined systemscolloidal silica and a polymer latex. The inclusion of surface transport processes markedly improves agreement between theory and the experimental data. For example, in situations where the standard theory underpredicts the measured dielectric increments by factors of 2 or 3, the dynamic Stern layer model yields results within 5% to 20% of the experimental data at frequencies in the kHz range.cess,

At present, several modalities exist for the preoperative staging of rectal lesions, including computed tomography (CT), body coil or endorectal coil magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS) done by rigid or flexible probes, and positron emission tomography (PET). Staging accuracy for CT ranges from 53% to 94% for T-stage accuracy and from 54% to 70% for N-stage accuracy. Improved CT accuracy is observed at higher disease stages. Body coil MRI has shownT-and N-stage accuracy ranging from 59% to 95% and 39% to 95 %, respectively. Endorectal coil MRI has shown improved T-and N-stage accuracy, with rates of 66% to 91% and 72% to 79%, respectively. The development of phased-array MRI, combining high spatial resolution with a larger field of view, offers promise to improve on these rates. EUS, considered the current gold standard, has shown T-stage accuracy ranging from 75% to 95%, with N-stage accuracy ranging from 65% to 80%. Flexible EUS probes have the advantage of being able to access and sample iliac nodes. Recent studies also suggest that three-dimensional EUS may provide greater accuracy than conventional two-dimensional EUS. Limited studies exist on the use of PET in primary tumor staging. PET may upstage disease in 8% to 24% of patients and has also been used in posttreatment restaging and surveillance. Postradiation edema, necrosis, and fibrosis seem to decrease restaging accuracy in all modalities. This article reviews the current literature about the staging accuracy of the various modalities and suggests a staging algorithm for rectal cancer.Accurate staging of rectal cancer is necessary to provide the optimal treatment strategy. Staging information includes extent of tumor involvement of the rectal wall and adjacent structures, presence or absence of adjacent lymphadenopathy, and determination of distant metastasis. Preoperative radiation therapy and total mesorectal excision (TME) are increasingly used in the treatment of locally advanced rectal cancer to reduce tumor recurrence. Recent data have shown that preoperative radiation therapy can reduce tumor recurrence from 27% to 11% (1). In addition, TME (a surgical technique that removes the rectum and surrounding mesorectal fat and perirectal lymph nodes and surrounding mesorectal fascia) has been shown to reduce postoperative recurrence to 10% without radiation therapy (2). A recent randomized controlled trial has shown that the combination of these techniques may reduce recurrence to 2.4% at 2 years compared with 8.2% with TME alone (3). Thus, accurate local staging information is paramount for stratifying patients who would benefit from neoadjuvant therapy as well as for predicting the surgical approach. Figure 1 illustrates major decision points that should be addressed in the staging process.At present, several modalities exist for the preoperative staging of rectal cancer: computed tomography (CT); magnetic resonance imaging (MRI) with traditional body, endorectal, or phased-array coils; endorectal ultrasonogra...