ELECTROKINETIC PHENOMENA : XIII. A COMPARISON OF THE ISOELECTRIC POINTS OF DISSOLVED AND CRYSTALLINE AMINO ACIDS

1. Although the isoelectric points of dissolved cystine, tyrosine, and aspartic acid molecules lie at widely differing pH values, the isoelectric points of the surfaces of these substances in the crystalline state are all near pH 2.3. This was found to be true in solutions of hydrochloric acid and in acetate buffers of approximately constant ionic strength. 2. When suspended in gelatin, tyrosine and cystine crystals adsorb the protein and attain a surface identical in behavior with gelatin-coated quartz or collodion particles. 3. Aluminum ions at low concentrations reduce the electric mobilities of tyrosine crystals to zero in a manner analogous to their effect on other surfaces. 4. Alkyl benzene droplets also have their electric mobility reduced to zero at low pH values but, unlike the amino acids, a change in sign was never noticed. 5. The mobility of tyrosine crystals is independent of crystal length between 2–100µ. Below this size the mobilities are decreased. 6. These results are discussed in connection with the concept of the general definition of the isoelectric point and the behavior of certain insoluble proteins such as wool and silk fibroin

THE ELECTRICAL CHARGE OF MAMMALIAN RED BLOOD CELLS

In Vol. 19, No. 4, March 20, 1936, page 603, in the eleventh line from the bottom of the page for "zj = 2, zjj = 1", read "zj = 1, zjj = 2". On the same page in the fourteenth line from the bottom of the page for "jj(HPO4-)" read "jj(HPO4--)"

HIV-Associated Hodgkin's Lymphoma: Prognosis and Therapy in the Era of cART

Patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) are at increased risk for developing Hodgkin's lymphoma (HL), a risk that has not decreased despite the success of combination antiretroviral therapy (cART) in the modern era. HIV-associated HL (HIV-HL) differs from HL in non-HIV-infected patients in that it is nearly always associated with Epstein-Barr virus (EBV) and more often presents with high-risk features of advanced disease, systemic “B” symptoms, and extranodal involvement. Before the introduction of cART, patients with HIV-HL had lower response rates and worse outcomes than non-HIV-infected HL patients treated with conventional chemotherapy. The introduction of cART, however, has allowed for the delivery of full-dose and dose-intensive chemotherapy regimens with improved outcomes that approach those seen in non-HIV infected patients. Despite these significant advances, HIV-HL patients remain at increased risk for treatment-related toxicities and drug-drug interactions which require careful attention and supportive care to insure the safe administration of therapy. This paper will address the modern diagnosis, risk stratification, and therapy of HIV-associated HL

Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling.

The tumor microenvironment (TME) exerts critical pro-tumorigenic effects through cytokines and growth factors that support cancer cell proliferation, survival, motility and invasion. Insulin-like growth factor-1 (IGF-1) and signal transducer and activator of transcription 3 (STAT3) stimulate colorectal cancer development and progression via cell autonomous and microenvironmental effects. Using a unique inhibitor, NT157, which targets both IGF-1 receptor (IGF-1R) and STAT3, we show that these pathways regulate many TME functions associated with sporadic colonic tumorigenesis in CPC-APC mice, in which cancer development is driven by loss of the Apc tumor suppressor gene. NT157 causes a substantial reduction in tumor burden by affecting cancer cells, cancer-associated fibroblasts (CAF) and myeloid cells. Decreased cancer cell proliferation and increased apoptosis were accompanied by inhibition of CAF activation and decreased inflammation. Furthermore, NT157 inhibited expression of pro-tumorigenic cytokines, chemokines and growth factors, including IL-6, IL-11 and IL-23 as well as CCL2, CCL5, CXCL7, CXCL5, ICAM1 and TGFβ; decreased cancer cell migratory activity and reduced their proliferation in the liver. NT157 represents a new class of anti-cancer drugs that affect both the malignant cell and its supportive microenvironment

Trapping Dynamics with Gated Traps: Stochastic Resonance-Like Phenomenon

We present a simple one-dimensional trapping model prompted by the problem of ion current across biological membranes. The trap is modeled mimicking the ionic channel membrane behaviour. Such voltage-sensitive channels are open or closed depending on the value taken by a potential. Here we have assumed that the external potential has two contributions: a determinist periodic and a stochastic one. Our model shows a resonant-like maximum when we plot the amplitude of the oscillations in the absorption current vs. noise intensity. The model was solved both numerically and using an analytic approximation and was found to be in good accord with numerical simulations.Comment: RevTex, 5 pgs, 3 figure

Effect of Non Gaussian Noises on the Stochastic Resonance-Like Phenomenon in Gated Traps

We exploit a simple one-dimensional trapping model introduced before, prompted by the problem of ion current across a biological membrane. The voltage-sensitive channels are open or closed depending on the value taken by an external potential that has two contributions: a deterministic periodic and a stochastic one. Here we assume that the noise source is colored and non Gaussian, with a $q$-dependent probability distribution (where $q$ is a parameter indicating the departure from Gaussianity). We analyze the behavior of the oscillation amplitude as a function of both $q$ and the noise correlation time. The main result is that in addition to the resonant-like maximum as a function of the noise intensity, there is a new resonant maximum as a function of the parameter $q$.Comment: Communication to LAWNP01, Proceedings to be published in Physica D, RevTex, 8 pgs, 5 figure

Multi-objective engineering shape optimization using differential evolution interfaced to the Nimrod/O tool

This paper presents an enhancement of the Nimrod/O optimization tool by interfacing DEMO, an external multiobjective optimization algorithm. DEMO is a variant of differential evolution – an algorithm that has attained much popularity in the research community, and this work represents the first time that true multiobjective optimizations have been performed with Nimrod/O. A modification to the DEMO code enables multiple objectives to be evaluated concurrently. With Nimrod/O’s support for parallelism, this can reduce the wall-clock time significantly for compute intensive objective function evaluations. We describe the usage and implementation of the interface and present two optimizations. The first is a two objective mathematical function in which the Pareto front is successfully found after only 30 generations. The second test case is the three-objective shape optimization of a rib-reinforced wall bracket using the Finite Element software, Code_Aster. The interfacing of the already successful packages of Nimrod/O and DEMO yields a solution that we believe can benefit a wide community, both industrial and academic

Testing for a Random Walk Structure in the Frequency Evolution of a Tone in Noise

Inference and hypothesis testing is constructed on the basis that a specific model holds for the data. To determine the veracity of conclusions drawn from such data analyses, one must be able to identify the presence of the assumed structure within the data. A model verification test is developed for the presence of a random walk-like structure for variations in the frequency of complex-valued sinusoidal signals measured in additive Gaussian noise. This test evaluates the joint inference of the random walk hypothesis tests found in economics literature that seek random walk behaviours in time series data, with an additional test to account for how the random walk behaves in frequency space.Comment: 11 pages, 13 figure