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The drug acetazolamide (C4H6N4O3S2) was studied using a simultaneous thermogravimetric–differential thermal analysis (TG–DTA) unit. The study covered the temperature range of ambient to 600 °C. The DTA showed a melting point of 258.5 °C followed by a three-stage decomposition. The TG–DTG plots clearly show the decomposition when subjected to heat treatment in a nitrogen atmosphere. A kinetic analysis of all stages was attempted, where a zero-order process appeared to be the best fit mechanism and plots of ln k versus T−1 show this. The values of Eact are shown to vary throughout each stage as the reaction progressed.

This study attempts to identify the degradative process which folic acid undergoes under thermal stress. In order to facilitate the process, the various pieces of the chemical structure, namely, p -amino benzoic acid (PABA), pterin and glutamic acid as both its d - and l -isomers were investigated as separate entities. These structured pieces were then compared to the composite folic acid degradative thermogram in order to identify the peaks seen and provide direction for the interpolation of the degradative mechanism [Thermal stability of folic acid and associated excipients, M.Sc. thesis, 2001]. It was observed that none of the structural pieces could be superimposed as assumed earlier, and hence, an attempt was made to identify the decomposition products using various analytical techniques such as infrared (IR) spectroscopy, mass spectroscopy (MS) and X-ray diffraction (XRD) which suggested that the glutamic acid fragment is lost first as evidenced by acid loss and amide enhancement in the IR spectra. The vitamin was ultimately degraded to carbon fragments and that further identification was not necessary.

There are a number of substances used to calibrate various instruments with benzoic acid being an IUPAC recommended calibration material. It has gained recognition as a reference material because it exhibits an ‘‘ideal’’ behavior. Hence, benzoic acid is often used to aid in determining the enthalpy of sublimation values for various organic substances. In this study, the thermal behavior of benzoic acid is observed from a simultaneous thermogravimetry–differential thermal analysis (TG–DTA) unit. A series of tests under various experimental conditions is performed, and the results allow for the determination of the enthalpy of sublimation values for benzoic acid. The purpose of this study is to investigate the influence of experimental parameters, such as sample preparation procedures, heating rates, atmospheric conditions, and gas flow rates, on the calculated enthalpy of sublimation values. Enthalpy of vaporization for benzoic acid was also calculated. # 2002 Elsevier Science B.V. All rights reserved.

The Langmuir equation was used to construct vapor pressure curves for the sublimation phase of nicotinic acid. Three different approaches were used to calculate the pressure values. In the first, the ‘k’ term of the Langmuir equation was eliminated by comparing the sample with the reference compound, in the second, the actual values of the ‘k’ term were used and in the third approach, the ‘k’ term was kept constant. The vapor pressure curve constructed using the actual values of ‘k’ was in close agreement with the first. This indicates that the ‘k’ term of the Langmuir equation cannot be assumed to be constant and the systematic variation in the values of the ‘k’ term with temperature has to be taken into consideration.

The three naturally occurring available carbonates in northwest Ohio are magnesite, calcite and dolomite. Dolomite is a double carbonate containing calcium and magnesium carbonate in equimolar concentrations. All three carbonates decompose via a single stage process in an atmosphere of nitrogen. The thermal behavior and the kinetics of decomposition were studied using the Arrhenius equation applied to solid-state reactions. It was found that calcite and dolomite supposedly decompose via a zero order mechanism while magnesite decomposes via a first order process. The energy of activation for the decomposition of magnesite, calcite and dolomite were 226.34, 192.50 and 175.05 kJ/mol, respectively. Similarly the ln A-values for magnesite, calcite and dolomite decomposition were 30.70, 20.73 and 18.76, respectively. Finally, the effect of procedural variables on the kinetic parameters of dolomite decomposition was investigated. The three procedural variables studied included flow rate, heating rate and sample size. The kinetic parameters and mechanism remain unaffected by a change in these variables. # 2002 Elsevier Science B.V. All rights reserved.

The thermal behavior of cinnamyl alcohol, which is used in the perfume industry to create a sweet, balsamic and hyacinth-like fragrance, was examined with a simultaneous thermogravimetric–differential thermal analysis (TG–DTA) unit. The sample was subjected to a controlled rising temperature regime under a regulated purge gas flow rate. The evaporation rates and coefficient of evaporation were calculated from TG–DTG data. From the DTG curve, it was found that the evaporation of cinnamyl alcohol is a zero-order process. The activation energy and enthalpy of vaporization for the evaporation process were determined by the use of the Arrhenius and Clausius–Clapeyron equations, respectively. The enthalpy value was calculated to be 68.10±0.84 kJ, while the energy of activation was found to be 66.34±0.84 kJ. The Langmuir equation was applied to the evaporation data, enabling the vapor pressure curves to be determined.

This study aims at providing a simple thermogravimetric method in estimating the vapor pressure characteristics using the Antoine equation as the analytical tool. The heat treatment for the majority of benzoic acid derivatives follows zero order rate processes that are in good correlation with their evaporation process. The optimum conditions for the rising temperature experiments were found when the heating rate was 10 8C/min in an atmosphere of dry nitrogen (100 ml/min). Methyl paraben was taken as the calibration compound since its Antoine constants are reported in literature and its selected thermodynamic parameters were evaluated using the Langmuir equation. The coefficient of vaporization k was determined to be 124525 � 0:8, with units being reported in the SI system. The corresponding vapor pressure plots were obtained for the remaining compounds that followed a zero order evaporation process and their Antoine constants were calculated using the Levenberg‐Marquardt least square curve fit method. # 2002 Elsevier Science B.V. All rights reserved.

Differential scanning calorimetry (DSC) is one of the important thermoanalytical techniques for preformulation studies of pharmaceutical substances. DSC studies can be used to characterize the melting behavior, crystallization, solid–solid transitions and chemical reactions of drugs. The attainment of proper results in a DSC experiment is dependant on a number of factors. The purpose of this study was to establish the appropriate condition for DSC performance. Factorial design and matrix analysis was used extensively in this study. The variables considered in this study were the sample size, heating rates, atmosphere, crucible type and relative humidity (RH). Two model drugs, benzoic acid (typical melting range: 121–123 °C, heat of fusion: 147 J/g) and vanillin (typical melting temperature: 81–83 °C, heat of fusion: 135 J/g) with sample size ranges of 3–5 and 10–12 mg were exposed to heating rates of 2 and 10 °C/min with atmospheres of air and nitrogen. The crucible types evaluated were open crucibles, crimped crucibles without pinhole and crimped crucible with pinhole. The samples were stored under 0, 25, 60 and 100% RH to evaluate the effect of RH on DSC performance. The study in this laboratory established a general protocol for DSC performance, which included the use of a small sample size range (3–5 mg), a low heating rate (2 °C/min), nitrogen as the atmosphere, crimped crucible without pinhole, and storage of the samples in a dry atmosphere (0% RH). Exceptions to the established protocols under various conditions are also discussed.

Thermogravimetric analysis is often used to evaluate the evaporation phenomenon of several substances. The present study was designed to characterize the vaporization characteristics of three essential oils; lemon oil, lavender oil and cinnamon oil and their several components. All three oils represent multi-component systems, whereas their main components represent single component systems. Linalyl acetate was used as the calibration compound and the coefficient of vaporization was obtained as 7×107 (SI system). The order of reaction was first determined for each of the compounds under study. Vapor pressure curves were then plotted using Langmuir and Antoine equations for the compounds, which represent single component systems, undergoing zero-order non-activated evaporation processes. The vapor pressure curves obtained were statistically quantified along with the calculations for the Antoine constants using SPSS version 10.0 software. The energies of activation for cinnamon oil, lemon oil and lavender oil were found to be 45.10, 33.2 and 33.9 kJ/mol, respectively.

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.

The objective of this study was to develop and analyze an analytical method in order to evaluate preformulation candidates by their thermodynamic parameters and evaporation characteristics. Ortho, meta and tere-phthalic acids were chosen as model compounds. The relative advantages and disadvantages of a rapid thermogravimetric method have been studied in detail, which would aid in the preformulation characterization for pharmaceuticals. Methyl paraben was taken as the model compound for calibration, as its evaporation characteristics are well known. Using the Antoine and the Langmuir equation for evaporation conjointly, the parameter k, known as the coefficient of evaporation was determined. The value for this constant was validated by three methods simultaneously. Previously the use of such methods for compounds having uninhibited zero order evaporation has been documented. In the present study, phthalic acid was chosen as the model compound since its evaporation is a two-step overlapping phenomenon. In this study we have shown the use of Pressure Differential Scanning Calorimetry in separating such simultaneous endothermic processes. The Clausius-Clapeyron equation seemingly has anomalous behavior for vapor pressure over high temperature ranges. In this study a modification of the equation has been suggested to take into account the changes in the heat capacities that result due to high temperature effects. This study aims at documenting a concise method for rapid pharmaceutical characterization and suggests modifications for some basic thermodynamic parameters over higher temperature ranges.

Background. Cumulative incidence of infections in the first year posttransplantation in adult patients has been well-described. Such description is less than complete for pediatric stem cell transplantation (SCT) patients. Further among those patients who have been infected, analysis of risk factors for infection has not been well-described for a large cohort of pediatric SCT patients. Methods. We conducted a retrospective cohort study of infections in the first year after SCT at Duke University Medical Center. We recorded all infections in the first year after transplantation. We determined incidences for 6 categories of infection: Gram-negative rods; Gram-positive cocci; yeast species; Aspergillus sp.; adenovirus; and cytomegalovirus. We determined incidences based on type of transplant and days post transplantation. We also completed bivariable and multivariable analysis of risk factors [neutropenia, graft vs. host disease (GVHD) and GVHD treatment] for infection type among those children who were infected. Results. We evaluated 510 transplants in 485 children. There were 584 infections in the first year after transplantation. During the first 30 days posttransplantation, type of transplantation did not predict incidence of infection or type of infection. After 30 days children who received unrelated cord blood transplant and matched unrelated donor transplant were at much higher risk of infection than were patients who received autologous, matched sibling or haploidentical transplant (P < 0.001). Patients who received unrelated cord blood or matched unrelated donor transplantation were at higher risk of aspergillosis (P = 0.002), candidiasis (P = 0.005) and adenovirus (P < 0.0001) but not cytomegalovirus (P = 0.18). In analysis of risk factors among those infected, patients with aspergillosis were more likely to have severe GVHD: multivariable 1 year risk ratio, 7.5; 95% confidence interval, 3.0,18.4. Neutropenia was more strongly associated with Gram-negative rod infection than any other type of infection. Conclusions. The incidence of infection immediately after transplantation did not differ significantly by type of transplant in this pediatric population. Type of transplant predicted increased incidence of infection 30 days posttransplantation and increased incidence of infection with several organisms traditionally associated with a high mortality rate in the transplant population.

Purpose To characterize a distinctive form of congenital stationary night blindness (CSNB). Design Observational case report. Participants A 30-year-old male with a history of night blindness, several members of his family, a patient with "complete" congenital stationary night blindness (CSNB1), and groups of age-similar control subjects. Methods Rod-system function was evaluated by measuring psychophysical dark-adapted thresholds, by recording dark-adapted electroretinograms (ERGs), and by fundus reflectometry. Cone-system function was evaluated by recording light-adapted ERGs, including those to sawtooth flicker, and by recording light-adapted visually evoked potentials (VEPs) to luminance increments and decrements. Main outcome measures Dark-adapted thresholds, ERGs, rhodopsin double densities, Goldmann visual fields, and VEPs. Results The patient's visual acuity, visual fields, and color vision were normal. His peripheral dark-adapted thresholds were rod-mediated but elevated by approximately 3 log units above normal. Rhodopsin double density and bleaching recovery were normal. His dark-adapted maximal-flash ERG showed a "negative" waveform, in which the b-wave was more reduced in amplitude than the a-wave, although the a-wave amplitude was also reduced. The rod photoreceptors contributed to the patient's dark-adapted ERGs, as illustrated by the unequal responses to cone-matched stimuli. The patient's cone-mediated thresholds for long-wavelength stimuli were within the normal range. However, his light-adapted brief-flash b-wave was abnormal in amplitude and implicit time. Selective abnormalities of the ON responses of the cone system were apparent in the patient's reduced b-wave amplitude to rapid-on flicker with a normal response to rapid-off flicker, and his prolonged VEP latencies to increments but not to decrements. Conclusions The overall pattern of findings distinguishes this patient from previously described forms of CSNB. The results suggest that two factors likely contribute to the patient's night blindness: (1) a rod phototransduction defect and (2) a postreceptoral defect. The results also indicate dysfunction within the cone ON pathway.

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.

Objective To compare the extent of intraocular straylight in carriers of choroideremia (CHM) and X-linked recessive retinitis pigmentosa (XLRP) to clarify further the relationship between photoreceptor cell degeneration and intraocular light scatter in retinal diseases. Design Prospective case-control study. Participants Six obligate carriers of CHM, 12 obligate carriers of XLRP, and 30 age-similar control subjects with normal vision. The controls had no posterior subcapsular (PSC) lens opacities, and the carriers had minimal or no PSC lens opacities, as assessed by slit-lamp biomicroscopy. Main outcome measures Straylight levels were measured using a van den Berg Straylightmeter. Visual acuity and Goldmann visual field area using a II/4e target were assessed for both eyes of each carrier. Electroretinogram (ERG) data were available on four of six carriers of CHM and all carriers of XLRP. The extent of retinal pigment epithelial degenerative changes was evaluated by fundus examination. Results All six carriers of CHM had typical fundus abnormalities with normal visual fields. Five of the six carriers of CHM had age-normal levels of intraocular light scatter, and one showed minimally elevated intraocular light scatter. The 12 carriers of XLRP had a spectrum of fundus abnormalities and varying severity of functional impairment as derived from visual field areas and ERG amplitudes. Seven of the 12 carriers of XLRP showed an elevated level of intraocular light scatter in at least one eye. The degree of straylight elevation above the normal mean age value was correlated significantly with both visual field area and amplitude of the maximal-intensity, dark-adapted ERG b-wave. Conclusions The carriers of XLRP who had evidence of photoreceptor cell dysfunction (as determined by visual field loss and reduced ERG amplitudes) had increased levels of intraocular straylight, whereas the carriers of CHM, who showed fundus abnormalities alone, in the absence of demonstrable photoreceptor cell dysfunction, had normal or minimally elevated levels. This finding supports the hypothesis that the increased levels of intraocular light scatter observed in some patients with hereditary retinal degenerations result from subclinical changes in the PSC region of the lens as a consequence of photoreceptor cell degeneration.

The purpose of this study was to identify the degradation products for folic acid which may form under thermal stress. An attempt was made to identify each of the decomposition products using various analytical techniques, such as infrared spectroscopy, mass spectroscopy, and X-ray diffraction, which suggested that the glutamic acid fragment of folic acid is lost first, as evidenced by acid loss and amide enhancement in the IR spectra. The vitamin was ultimately degrading to carbon fragments and further identification was not necessary.

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.

The Radon–Nikodym Theorem, in the context of probability measures, states that if all events having probability 0 under one probability measure also have probability 0 under a second measure, then the second measure is obtained by integrating some density function with respect to the first measure. Applications in probability and statistics arise in the contexts of likelihood functions, conditional expectation, Girsanov's formula, spectral measures and local time. The theorem and these applications are discussed. Keywords: density; Radon–Nikodym derivative; conditional expectation; likelihood; Girsanov's formula

Yearly, 33,000 cancer diagnoses in the US are attributed to human papillomavirus (HPV), with cervical cancer the most common. HPV is transmitted through sexual contact; HPV types 16 and 18 cause the majority of ano-genital cancers in men and women. HPV causes ∼100% of cervical cancers, ∼90% of anal cancers, and ∼50% of vaginal, vulvar, and penile cancers. HPV is also involved in ∼70% of oropharyngeal cancers (OPCs) in the US. The CDC recommends routine administration to all female (bivalent or quadrivalent vaccine) and male (quadrivalent vaccine) patients at 11-12 years of age; the series may be started as early as 9 years of age. Recent evidence suggests physicians do not universally recommend the vaccine to all adolescents. Additionally, parents may refuse the vaccine due to safety concerns as well as religious and moral beliefs related to onset of sexual debut. It has been suggested physicians should consider discussing HPV vaccine as a cancer prevention tool only, with less focus on the fact that transmission is caused by sexual activity. In this commentary we suggest physicians have a duty to warn parents and adolescents that OPCs may be transmitted through oral sex, which is often perceived as not constituting sexual activity.

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)

Suppository molds must be properly calibrated to ensure accurate dosing. There are often slight differences between molds and even in the cavities within a mold. A method is presented for the calibration of standard aluminum 6-, 12-, 50-, or 100-well suppository molds. Ten different molds were tested using water for volume calibration, and cocoa butter for standardization involving establishing the density factor. This method is shown to be straightforward and appropriate for calibrating suppository molds.

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.

We introduce the asymmetric random cluster (or ARC) model, which is a graphical representation of the Potts lattice gas, and establish its basic properties. The ARC model allows a rich variety of comparisons (in the FKG sense) between models with different parameter values; we give, for example, values (β, h) for which the 0‘s configuration in the Potts lattice gas is dominated by the “+” configuration of the (β, h) Ising model. The Potts model, with possibly an external field applied to one of the spins, is a special case of the Potts lattice gas, which allows our comparisons to yield rigorous bounds on the critical temperatures of Potts models. For example, we obtain 0.571 ≤ 1 − exp(−β c ) ≤ 0.600 for the 9-state Potts model on the hexagonal lattice. Another comparison bounds the movement of the critical line when a small Potts interaction is added to a lattice gas which otherwise has only interparticle attraction. ARC models can also be compared to related models such as the partial FK model, obtained by deleting a fraction of the nonsingleton clusters from a realization of the Fortuin-Kasteleyn random cluster model. This comparison leads to bounds on the effects of small annealed site dilution on the critical temperature of the Potts model.

A new titration method proposed by Huyhn et al., which directly measures the interparticular pore volume between the particles in a concentrated suspension, has been further investigated. It is expected that for an ideal powder with uniform spherical particles, the plot of weight versus the void volume should be a straight line passing through the origin. Glass beads, which are nonporous and expected to be ideal, were used in this study and the results were compared with the results of the experiments by Huyhn et al. Glass beads of different size ranges are used to study the effect of particle size on voidage. It was observed that the voidage increases with a decrease in particle size, However, the non-porous glass beads were also found not to be ideal.

Nicotinic acid belongs to the B group of vitamins and is often referred to as Vitamin B3. It is an essential component of a balanced diet and is prescribed as tablet, and in parenteral dosage forms in cases of vitamin deficiency. This study involves a preliminary preformulation study to assess whether nicotinic acid is a good candidate for tablet and capsule manufacture. The manufacturing process for solid dosage forms involves high energy-intensive processes, which mainly include grinding and compaction. The effect of these high-energy processes on the stability of nicotinic acid was evaluated using thermogravimetry (TG) as the primary analytical tool. The initial stage involved characterizing the thermal behavior of the material. It was found that nicotinic acid shows a solid-solid state phase transition, which is reversible. This transition appears as a small endothermic peak on the differential thermal analysis (DTA) curve, just before the dual sublimation-evaporation stage. This was followed by study...

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.

The heat treatment of parahydroxy benzoic acid esters follows zero order rate processes that are in good correlation with their evaporation process. Rising temperature experiments were performed and the optimum conditions were found when the heating rate was 10°C/min in an atmosphere of dry nitrogen, the flow rate of which was maintained at 100 mL/min. The Antoine constants for methyl paraben were substituted into the Antoine equation to get the corresponding vapor pressures that were then used in the Langmuir equation to obtain the value for the coefficient of evaporation k . The Eact value, obtained from the Arrhenius plot, was 75.1 kJ mol−1; the enthalpy of vaporization (ΔHvap) was calculated to be 77.9 kJ mol−1, in very close agreement with the Eact value. Using the Antoine and Langmuir equations, the value of k was experimentally determined to be 124525 ± 0.8, units being in the S.I. system. Taking the value of k to be independent of the substance, the corresponding vapor pressures were obtained for ...

Dolomite decomposes via a 2-stage mechanism in an atmosphere of CO2. The first stage of the decomposition was analyzed in depth using both isothermal and rising temperature kinetics. It was found that the first stage of decomposition follows the Avrami-Erofeev A2 mechanism for the isothermal experiments. However, for the rising temperature experiment, the reaction follows the Avrami-Erofeev A4 mechanism. The energy of activation (Ea) obtained for the isothermal experiments was determined to be 424.97 kJ/mol, while the value for the rising temperature experiment was 647.20 kJ/mol. Similarly, the ln A-value for the isothermal experiments was found to be 49.22, while the ln A-value for the rising temperature experiment was 74.20. The effect of procedural variables on the thermal behavior of dolomite in a nitrogen atmosphere is investigated. The program design variables include alterations in the flow rate, heating rate, grain size, and sample size. Out of these variables, heating rate, flow rate, and grain s...

Captopril is an antihypertensive drug currently being administered in tablet form. The thermal analysis study was carried out using a simultaneous TG–DTA unit. Both the isothermal and non-isothermal experiments are preformed to investigate the thermal degradation process of captopril in its natural state as a solid. The runs were performed in a flowing nitrogen atmosphere. Captopril melted at 106°C followed by decomposition. Based on the order of reaction, one method is used to identify the reaction mechanism in isothermal kinetics and two methods are used to identify the reaction mechanism in non-isothermal kinetics. These methods use the equations established by Avrami–Erofeev, Arrhenius and Freeman and Carroll. However, a kinetic analysis based on the “method of fit” using zero-order, first-order, and second-order equations showed that a first-order process gave a good fit for the Arrhenius plot at certain specific experimental conditions (i.e. very low sample mass). Overall, a second-order process followed by a first-order reaction for the main decomposition process of captopril showed an even better fit for the experiments. The possible reasons for this kinetic behavior are presented. There was up to 2% carbon remaining at 500°C. Thermal analysis was supplemented using Fourier Transform infrared spectroscopy (FTIR), X-ray diffraction and scanning electron microscopy (SEM) methods to identify the captopril with any degradation products which may have formed.

Allopurinol sublimates when subjected to thermogravimetry in a nitrogen atmosphere. The process is zero order and plots of ln k versus reciprocal temperature (K) give a value of 132.64 kJ mol −1 for the activation energy. On the basis that equilibrium is achieved at all temperatures the data is used to establish a plot of the vapor pressure curve versus temperature from which a Clausius–Clapeyron relationship can be used to establish the Δ H for sublimation. The method requires that the equipment is calibrated and data for p -aminobenzoic acid is used for this purpose.

The thermal analysis of basic magnesium carbonate has been investigated by thermogravimetry (TGA), derivative thermogravimetry (DTGA) and differential thermal analysis (DTA). The end product was magnesium oxide formed from the decomposition of magnesium carbonate. The composition of the samples studied varied, but the general formula that represented them was xMgCO3·yMg(OH)2·zH2O. In the present study, the thermal analysis of such magnesium carbonates in nitrogen, carbon dioxide and air was carried out at different heating rates and the origin of the exothermic peak was studied. Generally, the decomposition peaks were endothermic, but a persistent exothermic peak was noted, always accompanied by a very sharp drop in the TG curve, and the weight loss in this region may be significant. The exothermic DTA peak was found to be strongly influenced by the rate at which the samples were heated, sample size and atmospheric conditions.

The evaporation of methyl salicylate is studied using a simultaneous TG–DTA unit. The data are shown to be a zero order rate process. The activation energy calculated from the Kissinger and Ozawa methods as well as from the Arrhenius equations are shown to approximate the latent heat of vaporization calculated from the Clausius–Clapeyron equation. The activation energy values range from 52.5 to 60.4 kJ mol −1 for the Kissinger method, 52.2–63.6 kJ mol −1 for the Ozawa method and 47.2–50.3 kJ mol −1 for the Arrhenius equation.

Extensive studies have been done on the behavior of dolomite when subjected to a rising temperature program. In this study a literature survey was prepared related to the thermal decomposition of dolomite and the probable mechanisms proposed by various workers for the above reaction. Dolomite undergoes a two-stage decomposition in one atmosphere of carbon dioxide; while the same decomposition proceeds via a single step at lower partial pressures of carbon dioxide. The intermediate and final products for the two-stage decomposition of dolomite were isolated and identified using thermogravimetry and X-ray powder diffraction. On each of the isolated samples scanning electron microscopy was carried out. The intermediate products were found to be dolomite, calcite and periclase, while the final products were calcium oxide and periclase. Using these results a mechanism of thermal decomposition for dolomite is proposed.

Grinding is one of the most widely used unit processes in industry. The application of grinding to the pharmaceutical industry is investigated in detail. The process of grinding finds wide application because it leads to surface activation and particle size reduction. This objective is achieved by the application of energy. A lot of the applied energy is dissipated as heat. A number of pharmaceutical solids are known to be heat labile. Thus, the milling operation is a high-energy process, which could lead to detrimental effects on the structural pattern of the material being ground. This could be either due to the heat involved in the milling process or simply because of the high-energy impact of the milling medium. To investigate if grinding had detrimental effects, a detailed study was carried out using dolomite as the material to be ground. The unit cell of dolomite remained intact even after 24 h of grinding in a high-energy vibrating mill. This fact was confirmed using an X-ray powder diffraction methodology. It was found that although grinding did not deform the structural pattern of the dolomitic unit cell, a strain was however introduced in the structure. This strain appeared as a third peak in both the DTG and OTA curves This indicated the possible hazards of prolonged grinding and use of high-energy grinding equipment on the material exposed to the grinding process.

The evaporation of myristic acid [CH 3 (CH 2 ) 12 COOH] was investigated using a simultaneous TG–DTA unit over a temperature range of ambient to 300°C, in a flowing atmosphere of nitrogen at heating rates of 2, 4, 6, 8, 10, 15 and 20°C/min. The flow rates were varied from 50 to 350 ml/min. Kinetic plots for zero-order processes were constructed based on the Arrhenius equation and the Freeman and Carroll method. The activation energy for the evaporation process calculated from two methods was reported. The relationship between the rate of mass loss and the vapor pressure for myristic acid was estimated using the Langmuir and Antoine equations.

Characterization of formulation components in pre-formulation and formulation studies will be made easier if a rapid method to evaluate the evaporation characteristics of an ingredient in the formulation is developed. This study aims at providing a simple and rapid thermogravimetric method for estimating the vapor pressure characteristics using the Antoine equation as the analytical tool. The heat treatment for the majority of benzoic acid derivatives follows zero-order rate processes that are in good correlation with their evaporation process. The optimum conditions for the rising temperature experiments were found when the heating rate was 10 degrees C/min in an atmosphere of dry nitrogen (100 ml/min). Methyl paraben was taken as the calibration compound since its Antoine constants are reported in the literature, and its selected thermodynamic parameters were evaluated using the Langmuir equation. The coefficient of vaporization (k macro) was determined to be 124,525+/-0.8, with units being reported in the S.I. system. The corresponding vapor-pressure plots were obtained for the remaining compounds and their Antoine constants calculated.

We establish upper bounds for the spectral gap of the stochastic Ising model at low temperature in an N×N box, with boundary conditions which are “plus” except for small regions at the corners which are either free or “minus.” The spectral gap decreases exponentially in the size of the corner regions, when these regions are of size at least of order logN. This means that removing as few as O(logN) plus spins from the corners produces a spectral gap far smaller than the order N−2 gap believed to hold under the all-plus boundary condition. Our results are valid at all subcritical temperatures.

Hydroxy benzoic acids were subjected to rising temperature thermogravimetric analysis. After optimizing the procedural variables, the kinetics of decomposition was determined and methyl paraben was taken as the calibration compound to characterize the evaporation patterns for the ortho and meta derivatives. The Eact values for ortho, meta and para derivatives were 64.8, 78.2, and 119.1 kJ mol–1, respectively. The Antoine and Langmuir equations were utilized to determine the coefficient of evaporation k, which was 124525±0.8, units being in the SI system. The vapor pressure plots were generated for the ortho and meta derivatives; ΔHvap for these two compounds were obtained as 66.7 and 80.4 kJ mol–1, respectively.

We establish upper bounds for the spectral gap of the stochastic Ising model at low temperatures in an l×l box with boundary conditions which are not purely plus or minus; specifically, we assume the magnitude of the sum of the boundary spins over each interval of length l in the boundary is bounded by δl, where δ

Purpose To investigate the functioning in daily task performance of individuals with retinitis pigmentosa (RP). Goals were (1) to quantify the relationships among clinical tests of vision, self-reports, and evaluations of actual task performance to predict difficulty in these tasks; and (2) to validate self-report questionnaire data about daily task performance with observations and measurements of actual task performance conducted by a certified low-vision specialist. Design A cross-sectional study and survey. Participants Sixty-two individuals with RP (mean age, 37 years) participated in the study. Methods We obtained data about task performance from subjects' reports about their daily performance as assessed by a 53-item questionnaire and from a specialist's rating about actual ability on a 64-item battery of tasks, including ones similar to those assessed with the questionnaire. Main outcome measures Clinical measures of vision included visual acuity, visual fields using Goldmann perimetry, letter contrast sensitivity, and cone and rod electroretinogram (ERG) function. The questionnaire and functional tasks were clustered into three categories: "reading," "mobility," and "peripheral detection." Results Self-report was correlated significantly with actual task performance. Task performance was correlated significantly with clinical test performance. Moderate or worse difficulty in performance was observed only for visual acuity worse than 20/40; log contrast sensitivity less than 1.4; a visual field area smaller than 2000 deg 2 (area equivalent to a 50-degree diameter of visual field to the Goldmann II-4-e target); and ERG amplitudes less than 10 microvolts for 32-Hz light-adapted white flicker. Conclusions Despite the significant correlations, there remains variability in task performance that is unaccounted for in some individuals with low levels of clinical test performance. The assessment of actual task performance validated the use of self-reports in individuals with RP.

The effects of procedural variables on dolomite decomposition in carbon dioxide were investigated. The partial pressure of carbon dioxide causes dolomite decomposition to split into a two-stage process. It was observed that the first stage of dolomite decomposition is progressively displaced to higher temperatures with an increase in heating rate. However, the second stage is not affected significantly by changes in the heating rate. These studies also indicate that decrepitation analysis on dolomite in CO2 provides better information as compared to experiments in other atmospheres. The flow rate of the purge gas does not influence the thermal behavior of dolomite.

Infection with human papillomavirus is extremely common throughout the world. Almost 50% of sexually active young women are infected with human papillomavirus and although most infections are transient, a subset has the potential to progress to invasive cancer. During the last 20 years, our understanding of the human papillomavirus life cycle and the role of human papillomavirus in human cancer has dramatically increased. Recent technological advances in human papillomavirus detection have provided the means to detect the presence of human papillomavirus with great sensitivity. In the context of patient care, there is still substantial debate regarding the optimal diagnostic and prognostic use of information derived from hybrid capture or polymerase chain reaction-based detection. The inventory of available treatment options is growing somewhat slowly. The most promising advances are being made in the clinical evaluation of candidates for prophylactic vaccination. This review is focused on the current status and future directions of prevention, diagnosis and therapy.

The purpose of this study was to find a more efficient method for determining the porosity, or voids, using an insoluble powder in a pharmaceutical suspension. In a random arrangement of uniform spheres the only concern is with the limits of porosity existing within that collection. Theoretically, no equation can completely describe the physical properties of a sediment in a liquid medium without considering its particle size, size distribution, shape features, surface characteristics, etc. For the ideal case dealing with uniform spherical particles, it is expected that the plot of the weight of solid versus the volume of liquid used to fill the voids should be a straight line with zero intercept. A new titration method has been proposed to directly measure the immediate pore volume between particles in the suspension. Further investigation is required to determine its sensitivity such that it may provide a means of differentiating the nature of the particle–particle and particle–liquid attractive forces within a given pharmaceutical suspension system.

Sodium bicarbonate (NaHCO 3 ) is used as an anti-plaque agent in a variety of dental formulations. The aim of this study was to understand the active ingredient–excipient type of interactions in the solid state using thermal analysis. A simple formulation such as a the dental formulation was chosen as an example. Equivalent-ratio w/w binary, tertiary and quaternary mixtures of commercially obtained NaHCO 3 were prepared with solid excipients used in dental formulations. The thermal decomposition of NaHCO 3 was studied in the presence of these excipients, using thermogravimetric analysis (TGA) and differential thermal analysis (DTA). Apart from kinetic analysis, two other methods were developed during the course of this project to assess the solid state reactivity of NaHCO 3 . The reactivity of NaHCO 3 changed in the presence of other solid excipients. The methods developed during this project were successfully used in assessing the solid state reactivity of NaHCO 3 in the presence of other substances. It was concluded that these thermal analysis methods could also be applied to other substances for similar solid state studies.

The purpose of this study is to examine the thermal behavior of saturated fatty acids [CH3(CH2)nCOOH], where n varies from na 10 to na 16, during heating. The studies were performed over a temperature range of ambient temperature to 3508C in a flowing atmosphere of nitrogen, using a SDT 2960 simultaneous TGA‐DTA unit. The acids showed two endotherms due to melting at a lower temperature and vaporization at the higher temperature, which is a zero order process. The influence of flow rate and heating rate on the melting points is reported. The latent heat (DHevap) of vaporization process is calculated by the Antoine equation and the Clausius‐Clapeyron equation at different temperature ranges. The activation energy (Eact) was calculated from the rising temperature experiments, using the Arrhenius equation. These observations should be of use in the characterization of pharmaceutical excipients. # 1999 Elsevier Science B.V. All rights reserved.

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.

The heat treatment of an α-cellulose and a microcrystalline cellulose (Avicel®) in nitrogen gives a one-stage degradation to carbon. This degradation suffers a temperature transposition in the presence of pharmaceutical excipients, namely dibasic calcium phosphate, stearic acid, magnesium stearate, and silicon dioxide. It is possible to produce a kinetic evaluation of these thermal analysis studies in terms of a comparative method by constructing the theoretical TG trace of the binary mixture based on a presumed no-interaction between the two components. There is a variation in behavior to be noted in the different forms of cellulose, and also different values are shown for the Arrhenius parameters. Such variations are also noted in the Avicel® degradation in the presence of other materials. These observations should be of use in the characterization of pharmaceutical excipients. The Arrhenius parameters for α-cellulose degradation using D3 (three-dimensional diffusion) mechanism at the temperature range from 580 to 630 K are 289.32 kJ mol−1 and 1.85×1023 for Eact and A, respectively. The Arrhenius parameters for Avicel® degradation using F1 (first-order) mechanism at the temperature range from 562 to 604 K are 291.35 kJ mol−1 and 1.26×1025 for Eact and A, respectively.