Colloids with key-lock interactions: non-exponential relaxation, aging and anomalous diffusion

The dynamics of particles interacting by key-lock binding of attached biomolecules are studied theoretically. Experimental realizations of such systems include colloids grafted with complementary single-stranded DNA (ssDNA), and particles grafted with antibodies to cell-membrane proteins. Depending on the coverage of the functional groups, we predict two distinct regimes. In the low coverage localized regime, there is an exponential distribution of departure times. As the coverage is increased the system enters a diffusive regime resulting from the interplay of particle desorption and diffusion. This interplay leads to much longer bound state lifetimes, a phenomenon qualitatively similar to aging in glassy systems. The diffusion behavior is analogous to dispersive transport in disordered semiconductors: depending on the interaction parameters it may range from a finite renormalization of the diffusion coefficient to anomalous, subdiffusive behavior. We make connections to recent experiments and discuss the implications for future studies.Comment: v2: substantially revised version, new treatment of localized regime, 19 pages, 10 figure

Kinetic limitations of cooperativity based drug delivery systems

We study theoretically a novel drug delivery system that utilizes the overexpression of certain proteins in cancerous cells for cell specific chemotherapy. The system consists of dendrimers conjugated with "keys" (ex: folic acid) which "key-lock" bind to particular cell membrane proteins (ex: folate receptor). The increased concentration of "locks" on the surface leads to a longer residence time for the dendrimer and greater incorporation into the cell. Cooperative binding of the nanocomplexes leads to an enhancement of cell specificity. However, both our theory and detailed analysis of in-vitro experiments indicate that the degree of cooperativity is kinetically limited. We demonstrate that cooperativity and hence the specificity to particular cell type can be increased by making the strength of individual bonds weaker, and suggest a particular implementation of this idea. The implications of the work for optimizing the design of drug delivery vehicles are discussed.Comment: 4 pages, 4 figures, v3: minor revision

The 1980 solar maximum mission event listing

Information is contained on solar burst and transient activity observed by the Solar Maximum Mission (SMM) during 1980 pointed observations. Data from the following SMM experiments are included: (1) Gamma Ray Spectrometer, (2) Hard X-Ray Burst Spectrometer, (3) Hard X-Ray Imaging Spectrometer, (4) Flat Crystal Spectrometer, (5) Bent Crystal Spectrometer, (6) Ultraviolet Spectrometer and Polarimeter, and (7) Coronagraph/Polarimeter. Correlative optical, radio, and Geostationary Operational Environmental Satellite (GOES) x ray data are also presented. Where possible, bursts or transients observed in the various wavelengths were grouped into discrete flare events identified by unique event numbers. Each event carries a qualifier denoting the quality or completeness of the observations. Spacecraft pointing coordinates and flare site angular displacement values from Sun center are also included

Enhanced DNA binding affinity of RecA protein from Deinococcus radiodurans

© 2015 Elsevier B.V. Deinococcus radiodurans (Dr) has a significantly more robust DNA repair response than Escherichia coli (Ec), which helps it survive extremely high doses of ionizing radiation and prolonged periods of desiccation. DrRecA protein plays an essential part in this DNA repair capability. In this study we directly compare the binding of DrRecA and EcRecA to the same set of short, defined single (ss) and double stranded (ds) DNA oligomers. In the absence of cofactors (ATPγS or ADP), DrRecA binds to dsDNA oligomers more than 20 fold tighter than EcRecA, and binds ssDNA up to 9 fold tighter. Binding to dsDNA oligomers in the absence of cofactor presumably predominantly monitors DNA end binding, and thus suggests a significantly higher affinity of DrRecA for ds breaks. Upon addition of ATPγS, this species-specific affinity difference is nearly abolished, as ATPγS significantly decreases the affinity of DrRecA for DNA. Other findings include that: (1) both proteins exhibit a dependence of binding affinity on the length of the ssDNA oligomer, but not the dsDNA oligomer; (2) the salt dependence of binding is modest for both species of RecA, and (3) in the absence of DNA, DrRecA produces significantly shorter and/or fewer free-filaments in solution than does EcRecA. The results suggest intrinsic biothermodynamic properties of DrRecA contribute directly to the more robust DNA repair capabilities of D. radiodurans

Early carotid atherosclerosis and cardiac diastolic abnormalities in hypertensive subjects

Despite the fact that it is known that hypertension may be associated to early atherosclerosis manifestations, few data are to date available on the relationship between early carotid abnormalities and left ventricular diastolic dysfunction. To address this issue, 142 hypertensive patients (64 females and 78 males) younger than 55 years, at the first diagnosis of mild-to-moderate essential hypertension (WHO/ISH criteria), were selected from a database consisting of 3541 subjects referred to ultrasound cardiovascular laboratory in the last 5 years. Carotid intima-media thickness (IMT) was detected by high-resolution vascular ultrasound and left ventricular structure and function by the use of Doppler echocardiography. According to carotid IMT values, all patients were subgrouped into two groups consisting of 89 (62.6%) pts with IMT > or = 1 mm (A) and 53 (37.4%) pts with IMT < 1 mm (B). Our results show that isovolumic relaxation time (IVRT), deceleration time of E velocity (EDT) and left ventricular relative wall thickness (LV-RWT) were significantly (P < 0.05) higher in group A (IVRT 112 +/- 8.9 ms; EDT 288 +/- 21.8 ms; LV-RWT 0.40 +/- 0.08) than in group B (IVRT 92.3 +/- 4.6 ms; EDT 203.3 +/- 27.01 ms; LV- RWT 0.37 +/- 0.06). Moreover, the prevalence of left ventricular hypertrophy (LVH) was significantly (P < 0.01) higher in group A (30/89; 33.7%) than in group B (8/53; 15%). A positive correlation (P < 0.001) between IMT, EDT and IVRT was found only in hypertensives without LVH. These results are consistent with the indication that IMT evaluation has to be recommended both in hypertensive patients with LVH and in those without LVH, but with left ventricular diastolic dysfunction. This approach might improve the prognostic stratification of hypertensive subjects and it might be suitable to recognize the subset of patients at a higher risk of cardiovascular disease or events early

Minimally invasive approach to eliminate pyogenic granuloma using Er, Cr: YSGG laser

Backgroung. PG or granuloma pyogenicum is a common tumor like growth of the oral cavity that is considered to be of non-neoplastic nature, arising commonly as a result of constant low grade trauma and poor oral hygiene and in few instances because of hormonal disturbances. Since it is a benign lesion, choice of treatment is surgical excision with removal of underlying cause if any. A newer treatment modality using laser has been reported. Case report. A 16-year-old male patient reported to our sector of oral medicine with the chief complaint of intra-oral painless growth since four months. Past history and medical history did not reveal any relevant information. He was taking no medication and had no history of known drug allergy. On intra-oral examination smooth surfaced and lobulated growth of approximately 1.5 × 1 × 0.5 cm in size was present in the palate. The lesion was pedunculated and was freely movable over peduncle. The surface of the lesion showed non-omogenous red color whereas in certain area was covered by yellowish plaque like material. On palpation, growth was non-tender, nonfluctuant, hard and fibrous in consistency. Treatment plan comprising of excisional biopsy of the lesion using an Er, Cr: YSGG laser. An elliptical incision was made around the peduncle, the lesion was lifted along with the underlying periosteum from the bone surface and removed. Hemostasis was achieved with the same laser and healing was obtained for second intention. Excised specimen was preserved and sent for histopathological examination. At 7 days recall, the gingival tissues were healthy with successful healing. Conclusion. Excisional surgery is the treatment of choice for PG. The use of laser may be a valid approach for the excision of this lesion, as it is minimally invasive and offers many clinical advantages (minimal intra-operative bleeding,hemostasis, reduced times of healing)

The Elliptic Hall algebra and the deformed Khovanov Heisenberg category

We give an explicit description of the trace, or Hochschild homology, of the quantum Heisenberg category defined by Licata and Savage. We also show that as an algebra, it is isomorphic to "half" of a central extension of the elliptic Hall algebra of Burban and Schiffmann, specialized at $\sigma = \bar\sigma^{-1} = q$. A key step in the proof may be of independent interest: we show that the sum (over $n$) of the Hochschild homologies of the positive affine Hecke algebras $\mathrm{AH}_n^+$ is again an algebra, and that this algebra injects into both the elliptic Hall algebra and the trace of the $q$-Heisenberg category. Finally, we show that a natural action of the trace algebra on the space of symmetric functions agrees with the specialization of an action constructed by Schiffmann and Vasserot using Hilbert schemes.Comment: 49 pages, numerous figure

When and how to treat acute hepatitis C?

Background: Appropriate treatment of acute hepatitis C is still a matter of controversy due to the lack of large controlled trials. Aim: To assess the effectiveness of interferon as treatment for acute hepatitis C by meta-analysis. Methods: MEDLINE search (1985-2002) was supplemented with manual searches of reference lists. Studies were included if they were controlled trials comparing interferon to no treatment and if they included patients with either post-transfusion or sporadic acute hepatitis C. Twelve trials were analyzed (414 patients). The outcome assessed was the sustained virological response (SVR) rate (undetectable hepatitis C virus RNA in serum at least 6 months after cessation of therapy). Results: Interferon significantly increased the SVR (risk difference 49%; 95% confidence interval 32.9-65%) in comparison to no treatment. The risk difference of SVR increased from 5 to 90% when trials were ordered by increasing interferon weekly dose. Delaying therapy by 8-12 weeks after the onset of disease does not compromise the SVR rate. Conclusions: Current evidence is sufficient to recommend interferon treatment of patients with acute hepatitis C. A later initiation of therapy yields the same likelihood of response as early treatment. A daily induction dose during the 1st month is the best option of treatment. © 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved