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Recent designs have allowed hollow cathode gas plasma sources to be adopted for use in plasma-enhanced atomic layer deposition with the benefit of lower oxygen contamination for non-oxide films (a brief review of this is provided). From a design perspective, the cathode metal is of particular interest since—for a given set of conditions—the metal work function should determine the density of electron emission that drives the hollow cathode effect. However, we found that relatively rapid surface modification of the metal cathodes in the first hour or more of operation has a stronger influence. Langmuir probe measurements and hollow cathode electrical characteristics were used to study nitrogen and oxygen plasma surface modification of aluminum and stainless-steel hollow cathodes. It was found that the nitridation and oxidation of these metal cathodes resulted in higher plasma densities, in some cases by more than an order of magnitude, and a wider range of pressure operation. Moreover, it was initially thought that the use of aluminum cathodes would not be practical for gas plasma applications, as aluminum is extremely soft and susceptible to sputtering; however, it was found that oxide and nitride modification of the surface could protect the cathodes from such problems, possibly making them viable.

Cervical cancer adversely impacts African American communities. While disparities in incidence remain unclear, communities continue to use forums to increase cervical cancer education. The purpose of this paper is to examine the efficacy of using community forums to increase human papillomavirus vaccine (HPVV) and cervical cancer knowledge in African American communities. This study is a one-group pretest-posttest study design using a 17-item questionnaire to collect data from 412 participants in diverse communities. Our analyses revealed perceived knowledge increased significantly after the forums for African American participants. For African Americans, perceived knowledge prior to the forums was explained by gender, access to care, and trust in clinical trials. After the forum, perceived knowledge was associated with access to care and trust in vaccines. Participants who had health insurance reported higher perceived HPV and cervical cancer knowledge and greater trust in vaccines. This study found community forums that address the cultural and historical context of research mistreatment related to HPVV development and include diverse racial/ethnic representation of stakeholders may be a useful strategy to increase HPVV, and cervical cancer knowledge in African American communities.

Background Human papillomavirus (HPV)-associated subsequent malignant neoplasms (SMNHPV ) in childhood cancer survivors are poorly understood. Methods The cumulative risk of SMNHPV was assessed among 24,363 Childhood Cancer Survivor Study participants. Standardized incidence ratios (SIRs) and absolute excess risk were calculated using age-matched, sex-matched, and calendar year rates from the Surveillance, Epidemiology, and End Results program. Poisson regression models identified SMNHPV risk factors, evaluating relative SIRs (rSIR) and 95% confidence intervals (95% CIs). Results In total, 46 survivors developed an SMNHPV (median age, 31 years [range, 10-56 years]; median time from primary cancer, 21 years [range, 9-35 years]). SMNHPV sites included oropharynx (N = 44), anorectum (N = 6), uterine cervix (N = 2), and vulva (N = 2). The 33-year cumulative incidence was 0.3% (95% CI, 0.2%-0.4%), and the SIR was nearly 3-fold that of the general population (SIR, 2.86; 95% CI, 2.05-4.00). Female survivors were not at increased risk of cervical or vulvar cancers compared with the general population. All survivors had an elevated risk of oropharyngeal SMNHPV (males: SIR, 4.06; 95% CI, 2.37-6.97; females: SIR, 8.44; 95% CI 4.88-14.61) and anorectal SMNHPV (males: SIR, 13.56; 95% CI, 5.09-36.13; females: SIR, 9.15; 95% CI, 2.29-36.61). Males (vs females: rSIR, 1.99; 95% CI, 1.00-3.94); head, neck, and pelvic radiotherapy doses >3000 centigray (vs none: rSIR, 2.35; 95% CI, 1.11-4.97); and cisplatin-equivalent doses >400 mg/m2 (vs none: rSIR, 4.51; 95% CI, 1.78-11.43) were associated with increased SMNHPV SIRs in multivariable analysis. Conclusions Childhood cancer survivors are at increased risk for SMN in sites susceptible to HPV-associated malignancies. Further research examining HPV in the etiology of SMN and the promotion of HPV vaccination and surveillance guidelines for SMNHPV in cancer survivors is warranted.

For stationary first passage percolation in two dimensions, the existence and uniqueness of semi-infinite geodesics directed in particular directions or sectors has been considered by Damron and Hanson (Commun. Math. Phys., 2014), Ahlberg and Hoffman (preprint, 2016), and others. However the main results do not cover geodesics in the direction of corners of the limit shape $\mathcal{B}$, where two facets meet. We construct an example with the following properties: (i) the limiting shape is an octagon, (ii) semi-infinite geodesics exist only in the four axis directions, and (iii) in each axis direction there are multiple such geodesics. Consequently, the set of points of $\partial \mathcal{B}$ which are in the direction of some geodesic does not have all of $\mathcal{B}$ as its convex hull., 26 pages, 4 figures

Neuroblastoma is the second most common childhood tumor. Survival is poor even with intensive therapy. In a search for therapies to neuroblastoma, we assessed the oncolytic potential of Zika virus. Zika virus is an emerging mosquito-borne pathogen unique among flaviviruses because of its association with congenital defects. Recent studies have shown that neuronal progenitor cells are likely the human target of Zika virus. Neuroblastoma has been shown to be responsive to infection. In this study, we show that neuroblastoma cells are widely permissive to Zika infection, revealing extensive cytopathic effects (CPE) and producing high titers of virus. However, a single cell line appeared poorly responsive to infection, producing undetectable levels of non-structural protein 1 (NS1), limited CPE, and low virus titers. A comparison of these poorly permissive cells to highly permissive neuroblastoma cells revealed a dramatic loss in the expression of the cell surface glycoprotein CD24 in poorly permissive cells. Complementation of CD24 expression in these cells led to the production of detectable levels of NS1 expression after infection with Zika, as well as dramatic increases in viral titers and CPE. Complementary studies using the Zika virus index strain and a north African isolate confirmed these phenotypes. These results suggest a possible role for CD24 in host cell specificity by Zika virus and offer a potential therapeutic target for its treatment. In addition, Zika viral therapy can serve as an adjunctive treatment for neuroblastoma by targeting tumor cells that can lead to recurrent disease and treatment failure.

The availability of suppositories in Hungary, especially in clinical pharmacy practice, is usually provided by extemporaneous preparations. Due to the known advantages of rectal drug administration, its benefits are frequently utilized in pediatrics. However, errors during the extemporaneous manufacturing process can lead to non-homogenous drug distribution within the dosage units. To determine the root cause of these errors and provide corrective actions, we studied suppository samples prepared with exactly known errors using both cerimetric titration and HPLC technique. Our results show that the most frequent technological error occurs when the pharmacist fails to use the correct displacement factor in the calculations which could lead to a 4.6% increase/decrease in the assay in individual dosage units. The second most important source of error can occur when the molding excess is calculated solely for the suppository base. This can further dilute the final suppository drug concentration causing the assay to be as low as 80%. As a conclusion we emphasize that the application of predetermined displacement factors in calculations for the formulation of suppositories is highly important, which enables the pharmacist to produce a final product containing exactly the determined dose of an active substance despite the different densities of the components.

A union encounters forces which are of sufficient strength to override pressures to negotiate comparable settlements. To gain further insight into the nature of these forces and the union's reaction, the author interviewed union officials of the UAW in Detroit and made a study of 140 collective agreements carried on through the UAW in various industries in the same area., L'étude des conventions de travail signées par les représentants de UAW dans la région de Détroit permet de les classifier en deux catégories: celles des entreprises situées à l'intérieur de l'industrie de l'automobile et celles des entreprises situées à l'extérieur de cette industrie. Les facteurs qui expliquent l'écart dans les avantages obtenus dans la deuxième catégorie par rapport à la première sont les suivants:Tous ces facteurs jouent à des degrés différents dans la négociation de chacun des contrats. Et si l'on veut connaître les raisons pour lesquelles des contrats transiges par une même union s'écartent les uns des autres, il est nécessaire de jeter davantage de lumière sur chacun de ces facteurs.

Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening, provide an unprecedented opportunity to greatly reduce cervical cancer in the USA. Despite these advances, thousands of women continue to be diagnosed with and die of this highly preventable disease each year. This paper describes the initiatives and recommendations of national cervical cancer experts toward preventing and possibly eliminating this disease.In May 2011, Cervical Cancer-Free America, a national initiative, convened a cervical cancer summit in Washington, DC. Over 120 experts from the public and private sector met to develop a national agenda for reducing cervical cancer morbidity and mortality in the USA.Summit participants evaluated four broad challenges to reducing cervical cancer: (1) low use of HPV vaccines, (2) low use of cervical cancer screening, (3) screening errors, and (4) lack of continuity of care for women diagnosed with cervical cancer. The summit offered 12 concrete recommendations to guide future national and local efforts toward this goal.Cervical cancer incidence and mortality can be greatly reduced by better deploying existing methods and systems. The challenge lies in ensuring that the array of available prevention options are accessible and utilized by all age-appropriate women-particularly minority and underserved women who are disproportionately affected by this disease. The consensus was that cervical cancer can be greatly reduced and that prevention efforts can lead the way towards a dramatic reduction in this preventable disease in our country.

At certain temporal frequencies, the human cone flicker electroretinogram (ERG) contains multiple additional responses following the termination of a flicker train. The purpose of this study was to determine whether these poststimulus responses are a continuing response to the terminated flicker train or represent the oscillation of a resonant system. ERGs were recorded from 10 visually normal adults in response to full-field sinusoidally modulated flicker trains presented against a short-wavelength rod-saturating adapting field. The amplitude and timing properties of the poststimulus responses were evaluated within the context of a model of a second-order resonant system. At stimulus frequencies between 41.7 and 71.4 Hz, the majority of subjects showed at least three additional ERG responses following the termination of the flicker train. The interval between the poststimulus responses was approximately constant across stimulus frequency, with a mean of 14.4 ms, corresponding to a frequency of 69.4 Hz. The amplitude and timing characteristics of the poststimulus ERG responses were well described by an underdamped second-order system with a resonance frequency of 70.3 Hz. The observed poststimulus ERG responses may represent resonant oscillations of retinal ON bipolar cells, as has been proposed for electrophysiological recordings of poststimulus responses from retinal ganglion cells. However, further investigation is required to determine the types of retinal neurons involved in the generation of the poststimulus responses of the human flicker ERG.

Background. Many adolescents underutilize preventive services and are underimmunized. Methods. To promote medical homes and increase immunization rates, we conceptualized and implemented a 3-year, 8-school pilot school-located vaccination collaborative program. We sought community, parent, and school nurse input the year prior to implementation. We selected schools with predominantly Medicaid-enrolled or Medicaid-eligible students to receive Vaccines For Children stock vaccines. Nurses employed by a mass immunizer delivered these vaccines at participating schools 3 times a year. Results. Over 3 years, we delivered approximately 1800 vaccines at schools. School administrators, health centers, and neighboring private physicians generally welcomed the program. Parents did not express overt concerns about school-located vaccination. School nurses were not able to participate because of multiple school assignments. Obtaining parental consent via backpack mail was an inefficient process, and classroom incentives did not increase consent form return rate. The influenza vaccine had the most prolific uptake. The optimal time for administering vaccines was during regular school hours. Conclusions. Although school-located vaccination for adolescents is feasible, this is a paradigm shift for community members and thus accompanies challenges in implementation. High principal or school personnel turnover led to a consequent lack of institutional memory. It was difficult to communicate directly with parents. Because we were uncertain about the proportion of parents who received consent forms, we are exploring Internet-based and back-to-school registration options for making the consent form distribution and return process more rigorous. Securing an immunization champion at each school helped the immunization processes. Identifying a financially sustainable school-located vaccination model is critical for national expansion of school-located vaccination.

To document a novel NYX gene mutation in a patient with X-linked complete congenital stationary night blindness and to describe this patient's electroretinogram (ERG) characteristics.ERGs were recorded from a 17-year-old male with a previously unreported NYX mutation (819GA) that results in a missense codon change (Trp237Ter). ERGs were recorded in response to brief-flash stimuli, 6.33-Hz sawtooth flicker, and sinusoidal flicker ranging from 6.33-100 Hz. The omitted stimulus response (OSR) of the flicker ERG, which is thought to be generated within the ON-pathway, was also assessed.The patient's single-flash responses were consistent with previously documented NYX ERG characteristics, including a high-luminance flash response that was electronegative under dark-adapted conditions and a square-like a-wave followed by an abnormally shaped positive potential under light-adapted conditions, both of which are consistent with an ON-pathway deficit. Further evidence for an ON-pathway deficit included: (1) ERGs to rapid-on sawtooth flicker in which b-wave amplitude was reduced more than a-wave amplitude, and (2) responses to sinusoidal flicker that lacked the normal amplitude minimum and phase inflection near 12 Hz, ERG characteristics that are like those of patients with other NYX mutations. Novel findings included a pronounced amplitude attenuation for sinusoidal flicker at frequencies above approximately 50 Hz and an absent OSR, suggesting ON-pathway dysfunction at high frequencies.The substantial loss of ERG amplitude and apparent ON-pathway dysfunction at high temporal frequencies distinguish this patient with a Trp237Ter NYX mutation from those with other previously reported NYX mutations.

Background. Skin infections occur commonly and often present therapeutic challenges to practitioners due to the growing concerns regarding multidrug-resistant bacterial, viral, and fungal strains. The antimicrobial properties of zinc sulfate and copper sulfate are well known and have been investigated for many years. However, the synergistic activity between these two metal ions as antimicrobial ingredients has not been evaluated in topical formulations. Objective. The aims of the present study were to (1) formulate topical creams and gels containing zinc and copper alone or in combination and (2) evaluate the in vitro antibacterial activity of these metal ions in the formulations. Method. Formulation of the gels and creams was followed by evaluating their organoleptic characteristics, physicochemical properties, and in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus. Results. Zinc sulfate and copper sulfate had a strong synergistic antibacterial activity in the creams and gels. The minimum effective concentration was found to be 3 w/w% for both active ingredients against the two tested microorganisms. Conclusions. This study evaluated and confirmed the synergistic in vitro antibacterial effect of copper sulfate and zinc sulfate in a cream and two gels.

Organogels have emerged as an alternative carrier for small and macromolecules via transdermal, oral, rectal and ophthalmic routes. Pluronic lecithin organogels (PLO gels) are lecithin-based organogels widely used in compounding pharmacies as a vehicle for enhancing the transdermal permeability of many therapeutic drugs. However, the scientific and systematic evidence in support of how well PLO gels help in transdermal delivery is scanty. Recently, some clinical studies have reported nearly complete lack of bioavailability of certain topically administered drugs from PLO gels. The present review aims at summarizing gels and organogels, with a focus on the use of PLO gels in transdermal drug delivery. A special emphasis is placed on controversies looming over the use of PLO gels as a delivery platform for drugs via transdermal route. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

We study the intersection of two independent renewal processes, $\rho=\tau\cap\sigma$. Assuming that $\mathbf{P}(\tau_1 = n ) = \varphi(n)\, n^{-(1+\alpha)}$ and $\mathbf{P}(\sigma_1 = n ) = \tilde\varphi(n)\, n^{-(1+ \tilde\alpha)} $ for some $\alpha,\tilde \alpha \geq 0$ and some slowly varying $\varphi,\tilde\varphi$, we give the asymptotic behavior first of $\mathbf{P}(\rho_1>n)$ (which is straightforward except in the case of $\min(\alpha,\tilde\alpha)=1$) and then of $\mathbf{P}(\rho_1=n)$. The result may be viewed as a kind of reverse renewal theorem, as we determine probabilities $\mathbf{P}(\rho_1=n)$ while knowing asymptotically the renewal mass function $\mathbf{P}(n\in\rho)=\mathbf{P}(n\in\tau)\mathbf{P}(n\in\sigma)$. Our results can be used to bound coupling-related quantities, specifically the increments $|\mathbf{P}(n\in\tau)-\mathbf{P}(n-1\in\tau)|$ of the renewal mass function., Comment: 1 figure, 21 pages

PURPOSE To determine the relative contributions of optical and non-optical sources of intrinsic blur to variations in visual acuity (VA) among normally sighted subjects. METHODS Best-corrected VA of 16 normally sighted subjects was measured using briefly presented (59 ms) tumbling E optotypes that were either unblurred or blurred through convolution with Gaussian functions of different widths. A standard model of intrinsic blur was used to estimate each subject's equivalent intrinsic blur (σint) and VA for the unblurred tumbling E (MAR0). For 14 subjects, a radially averaged optical point spread function due to higher-order aberrations was derived by Shack-Hartmann aberrometry and fit with a Gaussian function. The standard deviation of the best-fit Gaussian function defined optical blur (σopt). An index of non-optical blur (η) was defined as 1 - σopt/σint. A control experiment was conducted on five subjects to evaluate the effect of stimulus duration on MAR0 and σint. RESULTS.: The logarithm of the minimum angle of resolution (logMAR₀) for the briefly presented E was correlated significantly with log σint (r = 0.95, p < 0.01), consistent with previous work. However, logMAR₀ was not correlated significantly with log σopt (r = 0.46, p = 0.11). For subjects with logMAR₀ equivalent to ~20/20 or better, logMAR₀ was independent of log η, whereas for subjects with larger logMAR₀ values, logMAR₀ was proportional to log η. The control experiment showed a statistically significant effect of stimulus duration on logMAR₀ (p < 0.01) but a non-significant effect on σint (p = 0.13). CONCLUSIONS The relative contributions of optical and non-optical blur to VA varied among the subjects and were related to the subject's VA. Evaluating optical and non-optical blur may be useful for predicting changes in VA following procedures that improve the optics of the eye in patients with both optical and non-optical sources of VA loss.

We study the solid-on-solid interface model above a horizontal wall in three dimensional space, with an attractive interaction when the interface is in contact with the wall, at low temperatures. There is no bulk external field. The system presents a sequence of layering transitions, whose levels increase with the temperature, before reaching the wetting transition., Comment: 61 pages, 6 figures. Miscellaneous corrections and changes, primarily in Section 4. Figure 5 added.

The purpose of this study was to define the quantitative relationship between the temporal characteristics of additive luminance noise and the properties of the spatial contrast sensitivity function (CSF). CSFs were obtained from two observers using Gabor patch targets of short duration that were added to white luminance noise with a range of root-mean-square contrasts (crms). The noise was either dynamic or static and was either of the same duration as the test target (synchronous) or of longer duration (asynchronous). For targets presented in asynchronous dynamic, synchronous dynamic, and synchronous static noise, the CSFs became increasingly band-pass with increasing crms, whereas the CSFs were low-pass at all levels of crms for targets presented in asynchronous static noise. For all noise types, the properties of the CSFs were well-predicted by the linear amplifier model (LAM), in which the signal energy at threshold (Et) is related linearly to noise spectral density (N). The fundamentally different characteristics of CSFs obtained in asynchronous static noise can be accounted for by a previous proposal that this noise type biases contrast sensitivity toward transient (inferred magnocellular) mechanisms. The other three modes of noise presentation appear to emphasize detection by sustained (inferred parvocellular) mechanisms.

When the eye is stimulated by a flickering light, the electroretinogram (ERG) and other electrophysiological responses in the visual pathway often exhibit period doubling. This phenomenon is manifested as an alternation in the shape of the response waveform from cycle to cycle, and also as spectral components at the half-fundamental frequency (F/2) and its odd multiples. Although period doubling has been described in humans as well as in other animals, its features in the rodent flicker ERG have not been characterized. We investigated the properties of period doubling in the rat cone flicker ERG elicited with full field, sinusoidal photic stimuli. Period doubling was observed when the temporal frequency of the stimulus was in the range of 20 to 30 Hz. The F/2 component of the Fourier spectrum of the ERG was more pronounced than its odd harmonics. The magnitude of the cycle-to-cycle variation in amplitude differed depending on whether measurements were based on peak-to-trough or trough-to-peak amplitudes, owing to the relative phase relationship between F/2 and F as a function of stimulus frequency. The frequency-response characteristics of period doubling varied with stimulus contrast, such that reducing the contrast shifted the peak F/2 amplitude to a lower stimulus frequency. Period doubling was evident in rat eyes in which PDA was administered intravitreally, indicating that the phenomenon can occur independently of OFF-pathway activity in the rat retina. The period doubling properties we observed in the flicker ERG response of the rat cone system provide constraints on the nature of the nonlinear feedback mechanism presumed to underlie the period doubling phenomenon.

We consider a polymer with configuration modeled by the path of a Markov chain, interacting with a potential $u+V_n$ which the chain encounters when it visits a special state 0 at time $n$. The disorder $(V_n)$ is a fixed realization of an i.i.d. sequence. The polymer is pinned, i.e. the chain spends a positive fraction of its time at state 0, when $u$ exceeds a critical value. We assume that for the Markov chain in the absence of the potential, the probability of an excursion from 0 of length $n$ has the form $n^{-c}\phi(n)$ with $c \geq 1$ and $\phi$ slowly varying. Comparing to the corresponding annealed system, in which the $V_n$ are effectively replaced by a constant, it is known that the quenched and annealed critical points differ at all temperatures for $3/22$, but only at low temperatures for $c3/2$ with arbitrary temperature we provide a new proof that the gap is positive, and extend it to $c=2$., Comment: 33 pages

Omitting a stimulus from a train of repetitive stimuli, by either interrupting or terminating the train, can elicit an electrophysiological response that occurs at the time appropriate for the omitted stimulus. This study investigated whether such an omitted stimulus response (OSR) is present in the flicker electroretinogram (ERG) of the human cone system. ERGs were recorded from 11 visually normal subjects in response to full-field sinusoidal flicker trains presented against a rod-desensitizing adapting field at frequencies ranging from 12.5 to 100 Hz. Recordings were synchronized with the onset of the stimulus trains, and the amplitude and relative delay of any additional ERG responses following the offset of the flicker train were analyzed. At stimulus frequencies below 35 Hz, the number of ERG responses always equaled the number of stimulus cycles. However, over the frequency range of 38.5 to 100 Hz, the ERG contained an extra response following flicker train offset. At stimulus frequencies from 38.5 to 62.5 Hz, there was a constant delay between the peak of the extra ERG response and the time at which the next stimulus would have occurred had the flicker train continued. This constant delay is characteristic of an OSR. In addition, an extra ERG response was apparent at these same stimulus frequencies if the flicker train was interrupted by omitting stimulus cycles from the middle of the train. The pattern of ERG findings is consistent with a recently proposed model of the OSR that attributes the phenomenon to a resonant oscillation in retinal bipolar cells.

OBJECTIVE The purpose of this study was to determine pediatricians' attitudes about the human papillomavirus (HPV) vaccine and to compare their attitudes with those expressed by the general public. METHODS Eight-hundred and fifty pediatricians from the American Academy of Pediatrics were surveyed, including general pediatricians (n = 450), and members of the sections of adolescent medicine (n = 200) and infectious diseases (n = 200). Pediatricians were asked to answer four items that had been included on a Wall Street Journal (WSJ) poll of the general public shortly after the HPV vaccine was approved by the Food and Drug Administration. RESULTS Of 752 eligible pediatricians, 373 (50%) responded. Compared to the general public, pediatricians were less likely to agree that routine Papanicolaou smears are a better strategy for preventing cervical cancer than HPV vaccination (12% vs 45%, P < 0.001), that abstinence programs are a better strategy for preventing the spread of HPV (17% vs 44%, P < 0.001), and that HPV vaccination may encourage sexual activity (4% vs 27%, P < 0.001). Pediatricians were more likely to support HPV vaccination without parental permission (77% vs 47%, P < 0.001). There were no differences between pediatricians based on gender. General pediatricians were more likely than pediatricians affiliated with the sections of infectious diseases and adolescent medicine to endorse abstinence programs over HPV vaccination (22% vs 16% and 8%, respectively, P = 0.01). CONCLUSION Pediatricians are much more supportive of HPV vaccination than the general public. Pediatricians should be aware of these differences when counseling patients and their families.

The electroretinogram (ERG) provides a noninvasive, objective measure of retinal function, and is one of the most widely used diagnostic tools in the study of visual disorders. Although rodents are often used in the study of retinal disease, the properties of the flicker ERG of the rodent retina have not been fully characterized. Here, we show that the fundamental response of the rat ERG to sine-wave flicker exhibited a low-pass pattern in the frequency range from 2 to 30 Hz, whereas the second harmonic (F2) showed a more complex frequency response relation. The F2 component represented only a small fraction of the ERG response at low temporal frequencies (below 12 Hz), but it made a substantial contribution to responses at high frequencies. The contrast-response relation was linear when tested with a low-frequency (6 Hz) stimulus, but saturated in response to a high-frequency (20 Hz) stimulus. After intravitreal injection of L-AP4, a specific blocker of the retinal ON pathway, the flicker responses elicited by either 6- or 20-Hz stimuli were greatly reduced in amplitude, whereas only a very slight enhancement was seen after the application of PDA, a drug that blocks retinal OFF-pathway activity. Based on the observed differences in the degree of non-linearity, and contrast-response properties of the rat flicker ERG at low and high frequencies, as well as the pharmacological results, we postulate that sustained and transient ON bipolar cells generate the flicker ERG responses elicited at low and high temporal frequencies, respectively.

We study i.i.d. sums $\tau_k$ of nonnegative variables with index $0$: this means $\mathbf{P}(\tau_1=n) = \varphi(n) n^{-1}$, with $\varphi(\cdot)$ slowly varying, so that $\mathbf{E}(\tau_1^\varepsilon)=\infty$ for all $\varepsilon>0$. We prove a local limit and local (upward) large deviation theorem, giving the asymptotics of $\mathbf{P}(\tau_k=n)$ when $n$ is at least the typical length of $\tau_k$. A recent renewal theorem by Nagaev [21] is an immediate consequence: $\mathbf{P}(n\in\tau) \sim \mathbf{P}(\tau_1=n)/\mathbf{P}(\tau_1 > n)^2$ as $n\to\infty$. If instead we only assume regular variation of $\mathbf{P}(n\in\tau)$ and slow variation of $U_n:= \sum_{k=0}^n \mathbf{P}(k\in\tau)$, we obtain a similar equivalence but with $\mathbf{P}(\tau_1=n)$ replaced by its average over a short interval. We give an application to the local asymptotics of the distribution of the first intersection of two independent renewals. We further derive downward moderate and large deviations estimates, that is, the asymptotics of $\mathbf{P}(\tau_k \leq n)$ when $n$ is much smaller than the typical length of $\tau_k$., Comment: 19 pages. We are grateful to V. Wachtel for bringing the result of Nagaev to our attention, and to an anonymous referee for pointing out a shorter proof of Theorem 1.3. Several changes were made accordingly

We introduce the pinning model on a quenched renewal, which is an instance of a (strongly correlated) disordered pinning model. The potential takes value 1 at the renewal times of a quenched realization of a renewal process $\sigma$, and $0$ elsewhere, so nonzero potential values become sparse if the gaps in $\sigma$ have infinite mean. The "polymer" -- of length $\sigma_N$ -- is given by another renewal $\tau$, whose law is modified by the Boltzmann weight $\exp(\beta\sum_{n=1}^N \mathbf{1}_{\{\sigma_n\in\tau\}})$. Our assumption is that $\tau$ and $\sigma$ have gap distributions with power-law-decay exponents $1+\alpha$ and $1+\tilde \alpha$ respectively, with $\alpha\geq 0,\tilde \alpha>0$. There is a localization phase transition: above a critical value $\beta_c$ the free energy is positive, meaning that $\tau$ is \emph{pinned} on the quenched renewal $\sigma$. We consider the question of relevance of the disorder, that is to know when $\beta_c$ differs from its annealed counterpart $\beta_c^{\rm ann}$. We show that $\beta_c=\beta_c^{\rm ann}$ whenever $ \alpha+\tilde \alpha \geq 1$, and $\beta_c=0$ if and only if the renewal $\tau\cap\sigma$ is recurrent. On the other hand, we show $\beta_c>\beta_c^{\rm ann}$ when $ \alpha+\frac32\, \tilde \alpha \beta_c^{\rm ann}$. We additionally consider two natural variants of the model: one in which the polymer and disorder are constrained to have equal numbers of renewals ($\sigma_N=\tau_N$), and one in which the polymer length is $\tau_N$ rather than $\sigma_N$. In both cases we show the critical point is the same as in the original model, at least when $ \alpha>0$., Comment: 51 pages, 1 figure

At temporal frequencies between approximately 30 and 70Hz, the flicker electroretinogram (ERG) of the cone system can exhibit an alternation in response amplitude from cycle to cycle that has been termed synchronous period doubling. This phenomenon has been attributed to a nonlinear feedback mechanism at an early retinal locus. The purpose of the present study was to define the effect of stimulus contrast on period doubling in order to better understand the nature of the underlying mechanism. ERGs were recorded from three visually normal subjects in response to sinusoidal flicker ranging from 20 to 100Hz, using stimulus contrasts of 37.7, 56.5, 75.4, and 94.2%. Period doubling was quantified as: (1) the amplitude of an harmonic component of the ERG waveform that was 1.5 times the stimulus frequency, and (2) the difference between the mean trough-to-peak amplitudes on even and odd cycles of the ERG waveform. Amplitudes were converted to responsivity by dividing by stimulus contrast. By both measures, subjects showed discrete regions of period doubling that were displaced to lower temporal frequencies as stimulus contrast was increased. The temporal frequency shift of period doubling with altered stimulus contrast can be accounted for quantitatively by postulating a neural threshold for the nonlinear feedback signal that is presumed to generate synchronous period doubling.

This study examined the relationship between the activation phase of cone phototransduction and the flicker electroretinogram (ERG) in 15 patients with retinitis pigmentosa (RP) and 12 age-equivalent, visually normal control subjects. Values of Rmp3 (maximum amplitude of P3, the massed cone photoreceptor response) and S (sensitivity of cone phototransduction) were derived from a delayed Gaussian model applied to the leading edge of the ERG a-wave. Fundamental amplitude and phase of the flicker ERG were derived from responses to sinusoidal flicker presented at temporal frequencies ranging from 7.8 to 100Hz. Patients with RP who had a reduced value of Rmp3 alone had an overall reduction in flicker ERG amplitude with a normal response phase across temporal frequency. Patients with RP who had a reduced value of S, whether or not Rmp3 was reduced, had the greatest amplitude reduction at temporal frequencies above 40Hz and phase lags across a range of temporal frequencies. At high temporal frequencies, the amplitude reduction of the flicker ERG was predicted by the product of Rmp3 and S for all of the subjects except the three patients with RP who had the lowest fundamental amplitudes. The results indicate that there is a systematic relationship between the derived parameters of the activation phase of cone phototransduction and the characteristics of the flicker ERG in patients with RP, although the phase changes in the flicker ERG were generally greater than predicted by the derived parameters alone.

In RNA interference (RNAi), double-stranded short interfering RNA (ds-siRNA) inhibits expression from complementary mRNAs. Recently, it was demonstrated that short, single-stranded antisense RNA (ss-siRNA) can also induce RNAi. While ss-siRNA may offer several advantages in both clinical and research applications, its overall poor activity compared with ds-siRNA has prevented its widespread use. In contrast to the poor gene silencing activity of native ss-siRNA, we found that the silencing activity of boranophosphate-modified ss-siRNA is comparable with that of unmodified ds-siRNA. Boranophosphate ss-siRNA has excellent maximum silencing activity and is highly effective at low concentrations. The silencing activity of boranophosphate ss-siRNA is also durable, with significant silencing up to 1 week after transfection. Thus, we have demonstrated that boranophosphate-modified ss-siRNA can silence gene expression as well as native ds-siRNA, suggesting that boranophosphate-modified ss-siRNAs should be investigated as a potential new class of therapeutic agents.

This study examined the extent to which letter optotypes and grating stimuli provide equivalent measures of contrast sensitivity under conditions designed to favor the magnocellular (MC) and parvocellular (PC) pathways. The contrast sensitivity functions (CSFs) of three visually normal observers were measured for Sloan letters and Gabor patches, using steady- and pulsed-pedestal paradigms to bias processing toward MC and PC pathways, respectively. CSFs for Gabor patches were low-pass for the steady-pedestal paradigm and band-pass for the pulsed-pedestal paradigm, in agreement with previous reports. However, CSFs for letters were low-pass for both testing paradigms. CSFs for letters restricted in frequency content by spatial filtering were equivalent to those for Gabor patches for both testing paradigms. Results indicate that conventional letter optotypes can provide a misleading measure of contrast sensitivity, especially under conditions emphasizing the PC pathway. The use of spatially band-pass filtered letters can provide a more appropriate evaluation of spatial contrast sensitivity while maintaining some of the potential advantages of letters.

We continue our study of colligative properties of solutions initiated in math-ph/0407034. We focus on the situations where, in a system of linear size $L$, the concentration and the chemical potential scale like $c=\xi/L$ and $h=b/L$, respectively. We find that there exists a critical value $\xit$ such that no phase separation occurs for $\xi\le\xit$ while, for $\xi>\xit$, the two phases of the solvent coexist for an interval of values of $b$. Moreover, phase separation begins abruptly in the sense that a macroscopic fraction of the system suddenly freezes (or melts) forming a crystal (or droplet) of the complementary phase when $b$ reaches a critical value. For certain values of system parameters, under ``frozen'' boundary conditions, phase separation also ends abruptly in the sense that the equilibrium droplet grows continuously with increasing $b$ and then suddenly jumps in size to subsume the entire system. Our findings indicate that the onset of freezing-point depression is in fact a surface phenomenon., Comment: 27 pages, 1 fig; see also math-ph/0407034 (both to appear in JSP)

The Ruther of today in his criticisms of organized labor may sound like the Lewis of the 1930's. But the issues within organized labor and the circumstances surrounding them are very different., Il semble que l'érudit et l'intellectuel aient abandonné depuis quelque temps les études institutionnelles du syndicalisme. En plus, la littérature écrite sur le syndicalisme a surtout insisté sur la non croissance du nombre de membres depuis environ dix ans. Cette stagnation est due à plusieurs facteurs :1 ) la majorité des secteurs où le syndicalisme puisait traditionnellement sa force sont maintenant presque tous syndiqués ;2) ces dits secteurs emploient relativement de moins en moins de travailleurs comparativement à la main-d'oeuvre totale ;3) dans les secteurs où l'emploi croît très rapidement, les travailleurs sont moins orientés vers le syndicalisme et en plus, il est très difficile de les organiser ;4) les changements dans l'emploi et les développements technologiques entraînent une mobilité occupationnelle qui rend la syndicalisation plus difficile ;5) les syndicats ainsi que les chefs syndicaux sont dans un certain état de léthargie ;6) l'opinion publique a changé au sujet du syndicalisme et la législation est devenue plus restrictive.Fait surprenant à noter, la place des syndicats dans la société américaine aujourd'hui est sensiblement la même qu'en 1920. Il serait très instructif de retracer brièvement les moyens employés par les syndicats pour presque revenir au point de départ en un si court laps de temps.En ce faisant, on pourra connaître les raisons de l'éloignement des syndicats d'une part, des érudits et des intellectuels d'autre part.Les années 20 furent suivies d'une période qui faussa notre pensée sociale, économique et politique. En économique, Keynes a détruit la conclusion classique à savoir que le plein emploi était le point d'équilibre naturel dans une économie de libre entreprise, avec, en plus, la philosophie de non-intervention de l'Etat comme conséquence. Ses idées ont trouvé des supporteurs parmi ces intellectuels qui étaient pris entre d'une part leurs préoccupations humanitaires pour les sous-développés et les désavantagés et d'autre part une certaine honorabilité intellectuelle face au désintéressement du gouvernement.L'application du New Deal ne représente pas la mise en pratique de la nouvelle conception économique. On dirait plutôt que ces mesures sont une recherche de solutions à des problèmes urgents par des politiciens pratiques. Quand on prend la peine de faire une analyse raisonnée à partir de la nouvelle conception économique, c'est souvent crû et naïf (par exemple, le préambule à la loi Wagner justifiait une augmentation de salaires par le simple pouvoir d'achat). Cette sorte de naïveté a aussi été la caractéristique du support intellectuel pour le syndicalisme dans les années 30. L'appui pour le COI provient de préoccupations humanitaires pour le travailleur désavantagé de l'industrie américaine : en plus, ce support provient de l'application fonctionnelle de la philosophie de Keynes qui prônait des transferts de revenus en faveur de la consommation croissante du salarié, de la demande aggregative et contribuant à une diminution du niveau de chômage. Avec cette conception de hausse, l'économique était naïve, mais l'entremelage de morale et de fonctionnalisme était confortable pour les intellectuels.Mais l'enthousiasme des intellectuels et l'appui général pour le travail organisé commença à baisser avant la fin des années 30. La deuxième guerre mondiale détourna la préoccupation humanitaire. Après la guerre, il y eût un certain intérêt dans le conflit de l'établissement du niveau de salaire, de profit et de revenu dans un contexte d'insécurité d'après guerre. Mais la guerre de Corée éteignit vite cet effort.La fusion FAT-COI était considérée comme une rationalisation institutionnelle issue d'une rivalité bureaucratique. Tout ceci gagna l'estime de plusieurs intellectuels qui, vingt ans plus tôt, se sentaient confortable dans leur support moral et fonctionnel du COI.En plus, la publication d'une pensée macro-économique plus compliquée ébranla les bases fonctionnelles du support syndical. Il devint apparent que le syndicalisme avait peu d'influence, sinon aucune, sur la distribution du revenu : et même s'il en avait, le gouvernement fédéral possédait des armes plus puissantes et prévisibles pour réduire le chômage. En plus, le fait de supporter le syndicalisme comme agent de transfert de revenu pour augmenter les dépenses et ainsi réduire le chômage, était une base transitoire de support syndical. En fait, une personne pouvait aussi logiquement s'opposer au syndicalisme afin de renverser la ligne de causalité dans le but de combattre l'inflation d'après guerre.L'expérience d'après guerre a façonnée une conception moins idéaliste du syndicalisme : en effet, on considéra alors les unions comme étant d'abord préoccupées par leur propre survie et agissant dans l'intérêt de leurs membres. Le pouvoir du syndicalisme d'affecter le bien être de ses membres est sujet à de fortes limitations dépendant dans une large mesure du pouvoir de marché et des fortunes économiques des employeurs. Aujourd'hui, on considère les unions comme étant des organisations à intérêt économique, privées de plusieurs préoccupations humanitaires. Les buts des campagnes d'organisation syndicale n'ont pas aujourd'hui un appui aussi sympathique que pendant les années 30.Voilà donc les ressemblances entre la position des syndicats aujourd'hui et leur position en 1920. Ainsi le Reuther d'aujourd'hui avec ses critiques du travail organisé peut ressembler au Lewis des années 30. Mais évidemment les résultats à l'intérieur du travail organisé et le contexte environnant sont très différents. Certaines parties du syndicalisme américain s'irritent à la suite de l'abandon de leur héritage humanitaire. Ils ont constamment une voix de sympathie pour les nouveaux « underdog » de la société et certains ont des programmes périphériques dont le but est le bien être général.Le 19e siècle s'avère être une leçon pour ce qui a trait à la faillite du syndicalisme de bien être et de la vitalité du syndicalisme d'affaire gomperien qui, encore, caractérise le mouvement du travail en Amérique.Les syndicats, aujourd'hui, trouvent leur succès dans des buts réformistes et humanitaires mieux atteints par une activité politique et par le support d'un parti politique : et ce parti doit considérer le syndicalisme comme une institution à intérêt économique. Il doit alors faire partie d'un processus gouvernemental afin de retenir et de restreindre le syndicalisme. Pour les syndicats, cette alliance politique doit être sujette à des tensions périodiques, comme on peut le noter depuis

We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20/15 to 20/40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform.

In RNA interference (RNAi), short double-stranded RNA (known as siRNA) inhibits expression from homologous genes. Clinical or pre-clinical use of siRNAs is likely to require stabilizing modifications because of the prevalence of intracellular and extracellular nucleases. In order to examine the effect of modification on siRNA efficacy and stability, we developed a new method for synthesizing stereoregular boranophosphate siRNAs. This work demonstrates that boranophosphate siRNAs are consistently more effective than siRNAs with the widely used phosphorothioate modification. Furthermore, boranophosphate siRNAs are frequently more active than native siRNA if the center of the antisense strand is not modified. Boranophosphate modification also increases siRNA potency. The finding that boranophosphate siRNAs are at least ten times more nuclease resistant than unmodified siRNAs may explain some of the positive effects of boranophosphate modification. The biochemical properties of boranophosphate siRNAs make them promising candidates for an RNAi-based therapeutic.

We consider boundary roughness for the ``droplet'' created when supercritical two-dimensional Bernoulli percolation is conditioned to have an open dual circuit surrounding the origin and enclosing an area at least $l^2$, for large $l$. The maximum local roughness is the maximum inward deviation of the droplet boundary from the boundary of its own convex hull; we show that for large $l$ this maximum is at least of order $l^{1/3}(\log l)^{-2/3}$. This complements the upper bound of order $l^{1/3}(\log l)^{2/3}$ known for the average local roughness. The exponent 1/3 on $l$ here is in keeping with predictions from the physics literature for interfaces in two dimensions., 28 pages, 1 figure (.eps file). See also http://math.usc.edu/~alexandr/

We study the depinning transition of the $1+1$ dimensional directed polymer in a random environment with a defect line. The random environment consists of i.i.d. potential values assigned to each site of $\mathbb{Z}^2$; sites on the positive axis have the potential enhanced by a deterministic value $u$. We show that for small inverse temperature $\beta$ the quenched and annealed free energies differ significantly at most in a small neighborhood (of size of order $\beta$) of the annealed critical point $u_c^a=0$. For the case $u=0$, we show that the difference between quenched and annealed free energies is of order $\beta^4$ as $\beta\to 0$, assuming only finiteness of exponential moments of the potential values, improving existing results which required stronger assumptions., Comment: 22 pages. Changes to Proposition 3.8 make Proposition 4.1 unnecessary; minor corrections made

Four non-polymeric plasticizers, propylene glycol, diethyl phthalate, triacetin, and glycerin have been subjected to rising temperature thermogravimetry for kinetic analysis and vaporization-based thermal stability evaluation. Since volatile loss of a substance is a function of its vapor pressure, the thermal stability of these plasticizers has been analyzed by generating vapor pressure curves using the Antoine and Langmuir equations. Unknown Antoine constants for the sample compounds, triacetin and glycerin have been derived by subjecting the vapor pressure curves to nonlinear regression. For the first time, the entire process of obtaining the unknown Antoine constants through thermogravimetry has been validated by developing an approach called the 'double reference method.' Based on this method, it has been possible to show that this technique is accurate even for structurally diverse compounds. Kinetic analysis on the volatilization of compounds revealed a predominant zero order process. The activation energy values for vaporization of propylene glycol, diethyl phthalate, triacetin, and glycerin, as deduced from the Arrhenius plots, have been determined to be 55.80, 66.45, 65.12, and 67.54 kJ/mol, respectively. The enthalpies of vaporization of the compounds have been determined from the Clausius-Clapeyron plots. Rising temperature thermogravimetry coupled with nonlinear regression analysis has been shown to be an effective and rapid technique for accurately predicting the vapor pressure behavior and thermal stability evaluation of volatile compounds.

The human papillomavirus (HPV) protein E2 possesses dual roles in the viral life cycle. By interacting directly with host transcription factors in basal keratinocytes, E2 promotes viral transcription. As keratinocyte differentiation progresses, E2 associates with the viral helicase, E1, to activate vegetative viral DNA replication. How E2's major role switches from transcription to replication during keratinocyte differentiation is not understood, but the presence of a TATA site near the viral origin of replication led us to hypothesize that TATA-binding protein (TBP) could affect HPV replication. Here we show that the C-terminal domain of TBP (TBPc) is a potent inhibitor of E2-stimulated HPV DNA replication in vitro (50% inhibitory concentration = 0.56 nM). Increasing the E1 concentration could not overcome TBPc inhibition in replication assays, indicating that TBPc is a noncompetitive inhibitor of E1 binding. While direct E2-TBPc association could be demonstrated, this interaction could not fully account for the mechanism of TBPc-mediated inhibition of viral replication. Because E2 supports sequence-specific binding of E1 to the viral ori , we proposed that TBPc antagonizes E1- ori association indirectly through inhibition of E2-DNA binding. Indeed, TBPc potently antagonized E2 binding to DNA in the absence ( K i = 0.5 ± 0.1 nM) and presence ( K i = 0.6 ± 0.3 nM) of E1. Since E2 and TBPc cannot be coadjacent on viral sequences, direct DNA-binding competition between TBPc and E2 was responsible for replication inhibition. Given the ability of TBPc to inhibit HPV DNA replication in vitro and data indicating that TBPc antagonized E2- ori association, we propose that transcription factors regulate HPV DNA replication as well as viral transcription.

To determine the temporal response characteristics of the mouse cone electroretinogram (ERG), we recorded responses to high contrast sinusoidal stimuli ranging from 2 to 52 Hz. The largest response amplitudes obtained from wild-type (WT) mice occurred at stimulus frequencies below 10 Hz, and cone ERG amplitude declined progressively with increasing stimulus frequency above that level. In comparison, human responses recorded under the same stimulus and recording conditions displayed maximal responses to stimulus frequencies near 4 and 40 Hz, and a pronounced dip at 12 Hz. Responses were also obtained from nob ( no b-wave) mice, which lack ERG contributions from depolarizing bipolar cells (DBCs). At low temporal frequencies, nob cone ERGs were smaller than those of WT mice and had a different waveform. As temporal frequency increased, nob and WT responses became more similar and came into register at the highest temporal frequencies. To evaluate the contribution of the DBC pathway to the mouse cone ERG, nobresponses were vector-subtracted from those of WT mice. The derived DBC response was maximal at low stimulus frequencies and fell sharply as stimulus frequency increased. These results indicate that the mouse cone ERG is more linear than the primate response and that the temporal response of the mouse outer retina is tuned to much lower frequencies than that of primate.

School-located vaccination (SLV) has a long history in the United States and has successfully contributed to lower morbidity and mortality due to vaccine-preventable diseases.1 Historically, SLV efforts, which tended to be single-vaccine programs intended to provide catch-up immunization to a defined school-age cohort or were implemented in response to an outbreak, were unfunded, funded by local health department, or were funded by industry or federal grants. The growing palette of vaccines recommended for routine use in adolescents along with limited success of office-based adolescent immunization create a compelling argument for the creation of financially sustainable SLV programs. An arguably significant barrier to both office-based and school-located adolescent immunization is the modest reimbursement rates afforded to immunizers. Because the immunization promotion and consent process is expensive, these costs must be reduced to a minimum to reach financial viability. Although there are challenges to creating a financially sustainable SLV program coordinated by an academic medical center, (AMC), the ability of AMCs to bill private and public insurers, the nonprofit status of medical centers, the allowances for faculty for academic pursuit, and the substantial infrastructure already present make AMCs a potentially practical site for the administration of SLV programs. Alternatively, as health departments throughout the nation continue to explore methods for billing private insurance, we may find health departments to be uniquely suited for coordinating the administration and billing of these services.

We study the path properties of a random polymer attracted to a defect line by a potential with disorder, and we prove that in the delocalized regime, at any temperature, the number of contacts with the defect line remains in a certain sense "tight in probability" as the polymer length varies. On the other hand we show that at sufficiently low temperature, there exists a.s. a subsequence where the number of contacts grows like the log of the length of the polymer., Published in at http://dx.doi.org/10.1214/13-AAP930 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org)

For a family of bond percolation models on Z^{2} that includes the Fortuin-Kasteleyn random cluster model, we consider properties of the ``droplet'' that results, in the percolating regime, from conditioning on the existence of an open dual circuit surrounding the origin and enclosing at least (or exactly) a given large area A. This droplet is a close surrogate for the one obtained by Dobrushin, Koteck\'y and Shlosman by conditioning the Ising model; it approximates an area-A Wulff shape. The local part of the deviation from the Wulff shape (the ``local roughness'') is the inward deviation of the droplet boundary from the boundary of its own convex hull; the remaining part of the deviation, that of the convex hull of the droplet from the Wulff shape, is inherently long-range. We show that the local roughness is described by at most the exponent 1/3 predicted by nonrigorous theory; this same prediction has been made for a wide class of interfaces in two dimensions. Specifically, the average of the local roughness over the droplet surface is shown to be O(l^{1/3}(\log l)^{2/3}) in probability, where l = \sqrt{A} is the linear scale of the droplet. We also bound the maximum of the local roughness over the droplet surface and bound the long-range part of the deviation from a Wulff shape, and we establish the absense of ``bottlenecks,'' which are a form of self-approach by the droplet boundary, down to scale \log l. Finally, if we condition instead on the event that the total area of all large droplets inside a finite box exceeds A, we show that with probability near 1 for large A, only a single large droplet is present., Comment: 72 pages

Using yeast forward and reverse two-hybrid analyses, we have discovered that the replication terminator protein Tus of Escherichia coli physically interacts with DnaB helicase in vivo . We have confirmed this protein–protein interaction in vitro . We show further that replication termination involves protein–protein interaction between Tus and DnaB at a critical region of Tus protein, called the L1 loop. Several mutations located in the L1 loop region not only reduced the protein–protein interaction but also eliminated or reduced the ability of the mutant forms of Tus to arrest DnaB at a Ter site. At least one mutation, E49K, significantly reduced Tus–DnaB interaction and almost completely eliminated the contrahelicase activity of Tus protein in vitro without significantly reducing the affinity of the mutant form of Tus for Ter DNA, in comparison with the wild-type protein. The results, considered along with the crystal structure of Tus– Ter complex, not only elucidate further the mechanism of helicase arrest but also explain the molecular basis of polarity of replication fork arrest at Ter sites.

The current models that have been proposed to explain the mechanism of replication termination are (i) passive arrest of a replication fork by the terminus (Ter) DNA-terminator protein complex that impedes the replication fork and the replicative helicase in a polar fashion and (ii) an active barrier model in which the Ter-terminator protein complex arrests a fork not only by DNA-protein interaction but also by mechanistically significant terminator protein-helicase interaction. Despite the existence of some evidence supporting in vitro interaction between the replication terminator protein (RTP) and DnaB helicase, there has been continuing debate in the literature questioning the validity of the protein-protein interaction model. The objective of the present work was two-fold: (i) to reexamine the question of RTP-DnaB interaction by additional techniques and different mutant forms of RTP, and (ii) to investigate if a common domain of RTP is involved in the arrest of both helicase and RNA polymerase. The results validate and confirm the RTP-DnaB interaction in vitro and suggest a critical role for this interaction in replication fork arrest. The results also show that the Tyr33 residue of RTP plays a critical role both in the arrest of helicase and RNA polymerase.

We used a motion coherence paradigm to test the hypothesis that patients with retinitis pigmentosa (RP) have difficulty discriminating the direction of spatial displacements because of a random loss of motion-sensitive units owing to cone photoreceptor dropout. Minimum ( D min ) and maximum ( D max ) displacement thresholds of patients with typical RP or Usher syndrome were compared with those of age-similar, visually normal subjects. Two-frame random dot cinematograms were used, in which a group of target dots, which comprised 40–100% of the dot array in steps of 20%, were displaced in one of four directions, whereas the non-target dots were randomly repositioned between frames. Reducing the dot coherence in this way increased D min and reduced D max for both the RP patients and control subjects. Furthermore, the displacement thresholds of the RP patients were displaced laterally from normal along a log coherence axis, consistent with the hypothesis that the patients had a reduced effective (intrinsic) coherence. However, the displacement thresholds of control subjects, when measured at a reduced coherence, did not mimic those of RP patients at full coherence when both groups were tested with a range of dot contrasts and dot areas. These apparently discrepant findings can be reconciled if it is assumed that the patients’ effective coherence varies with stimulus visibility.