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Irreversible electroporation (IRE) is used clinically as a focal therapy to ablate solid tumors. A critical disadvantage of IRE as a monotherapy for cancer is the inability of ablating large tumors, because the electric field strength required is often too high to be safe. Previous reports indicate that cells exposed to certain cationic small molecules and surfactants are more vulnerable to IRE at lower electric field strengths. However, low-molecular-weight IRE sensitizers may suffer from suboptimal bioavailability due to poor stability and a lack of control over spatiotemporal accumulation in the tumor tissue. Here, we show that a synthetic membranolytic polymer, poly(6-aminohexyl methacrylate) (PAHM), synergizes with IRE to achieve enhanced cancer cell killing. The enhanced efficacy of the combination therapy is attributed to PAHM-mediated sensitization of cancer cells to IRE and to the direct cell killing by PAHM through membrane lysis. We further demonstrate sustained release of PAHM from embolic beads over 1 week in physiological medium. Taken together, combining IRE and a synthetic macromolecular sensitizer with intrinsic membranolytic activity and sustained bioavailability may present new therapeutic opportunities for a wide range of solid tumors.

A biodegradable amphiphilic liquid polymer was designed to form self-emulsifying nanodroplets in water for delivering poorly soluble drugs. The polymer was composed of multiple short blocks of poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) connected through acid-labile acetal linkages. With an overall average molecular weight of over 18 kDa, the polymer remained as a viscous liquid under room and physiological temperatures. Dispersing the polymer in an aqueous buffer gave rise to highly stable micelle-like nanodroplets with an average size of approximately 15-20 nm. The nanodroplet dispersions underwent reversible temperature-sensitive aggregation with cloud points ranging from 45 to 50 °C, depending on polymer concentration. Nuclear magnetic resonance (NMR) and dynamic light scattering analyses revealed that while the nanodroplets were stable at pH 7.4 for several days, hydrolysis of the acetal linkages in the polymer backbone was much accelerated under mildly acidic pH 5.0, resulting in the formation of large microdroplets. Nile red (NR), a poorly water-soluble fluorophore, can be solubilized in the nanodroplets, and efficient intracellular delivery of NR was achieved. The hydrophobic indocyanine green (ICG) was also encapsulated in the nanodroplets. Near-infrared (NIR) fluorescence imaging and in vivo biocompatibility of the ICG-loaded nanodroplets were demonstrated in mice. In summary, the self-emulsifying nanodroplets of amphiphilic liquid polymer would be a promising material system for poorly soluble drug delivery and imaging in vivo.

Water pollution by heavy metal ions is a critical threat to public health. To remove the heavy metal pollutants from large waterbodies, we have synthesized a biocompatible, cost-effective, metal ion non-specific, and ethylenediaminetetraacetic acid (EDTA)-inspired polydentate hydrogel with exceptionally high adsorption capacity and reusability. The hydrogel was synthesized by the transamidation reaction between hydrolyzed polyacrylamide and branched polyethylenimine (BPEI). The mechanical strength of the synthesized hydrogel displayed an increasing trend with the wt % of the cross-linker (BPEI) and achieved a maximum storage modulus (Gmax') of 1093 Pa. Scanning electron microscopy revealed a porous network structure of the hydrogel (pore size: 30-70 μm), resulting in a very high swelling ratio of 5800%. The porous hydrogel manifested the maximum adsorption capacity of 482.2 mg/g when adsorbing from a mixture of metal ions (Cr3+, Cu2+, Zn2+, Cd2+, Hg2+, and Pb2+), higher than any EDTA-grafted material known to date. The high adsorption capacity of the hydrogel was attributed to the existence of numerous EDTA-mimicking coordinating functional groups, as confirmed by X-ray photoelectron spectroscopy. In addition, the hydrogel showed the self-healing property and preserved more than 85% adsorption efficiency even after five cycles of reuse. Furthermore, the hydrogels showed no or moderate toxicity toward mammalian cells.

The objective of this study is to develop a simple biopolymer platform of mucoadhesive wafers that enables effective sublingual delivery and preservation of protein vaccines. The wafers were composed of a series of binary polymer blends of carboxymethylcellulose (CMC) and alginate (ALG). Varying the ratio between CMC and ALG resulted in wafers with different microstructure, mechanical properties, disintegration time, and release kinetics of model compounds. Wafers with high CMC content were highly mucoadhesive to sublingual mucosal tissue and could withstand extensive washing, leading to improved protein permeation into the tissue. On the other hand, wafers with high ALG content were not only mechanically robust, but also able to protect a model enzyme (β-galactosidase) against lyophilization and heat challenge. HIV gp140 protein loaded in wafers of the optimal composition could be stored and transported without cold chain, while maintaining antigen-specific immunogenicity after sublingual vaccination in mice. These findings established that the CMC/ALG binary blend polymer wafers have the potential to improve the sublingual delivery and storage stability of protein-based vaccines.

Basin type solar still is a simple device which can be used for fresh water production. The main drawback of a conventional basin solar still is the low amount of distilled water production per unit area which makes the single-basin solar still uneconomical. In inclined still, higher surface area and thin water surface are its advantages and maintaining continuous wetness along the inclined surface and loss of heat through raw water drain are the problems. This work reviews different methods used to improve the effectiveness on the inclined solar still so far by different researchers and compare their performances.

The consumption of fibers is associated with many health benefits, such as a reduction of cardiovascular and gastrointestinal diseases, control of body weight, and prevention of diabetes. Despite the widespread use of fiber supplements such as capsules or tablets, there is an almost complete lack of information concerning the technological properties of functional fibers used in nutraceutical formulations. The aim of this work was to characterize the technological properties of citrus fibers necessary for their use as a processing aid in tableting. The results obtained showed that citrus fibers share many properties of other polysaccharides used as tableting excipients, such as thermal behavior and compaction mechanism, together with an appreciable tabletability. However, the most interesting properties resulted from their disintegration power. Citrus fibers behaved in a similar manner to the well-known super disintegrant croscarmellose sodium and resulted to be little susceptible to their concentration, to lubricant type, and lubricant concentration. Thus, this work supports the idea of a potential use of citrus fibers as “active” substances and processing aid in the tableting of nutraceutical products and also as functional excipient in pharmaceutical tablets formulation.

Dual functional unimolecular micelles based on a pH-responsive amphiphilic star polymer β-CD-(PLA-b-PDMAEMA-b-PEtOxMA)21 have been developed for the co-delivery of imiquimod and plasmid DNA to dendritic cells. The star polymer with well-defined triblock arms was synthesized by combining activator regenerated by electron-transfer atom-transfer radical polymerization with ring-opening polymerization. Dissipative particle dynamics simulation showed that core-mesophere-shell-type unimolecular micelles could be formed. Imiquimod-loaded micelles had a drug loading of 1.6 wt % and a larger average size (28 nm) than blank micelles (19 nm). The release of imiquimod in vitro was accelerated at the mildly acidic endolysosomal pH (5.0) in comparison to physiologic pH (7.4). Compared with blank micelles, a higher N:P ratio was required for imiquimod-loaded micelles to fully condense DNA into micelleplexes averaging 200–400 nm in size. In comparison to blank micelleplexes, imiquimod-loaded micelleplexes of the same N:P ratio displayed similar or slightly higher efficiency of gene transfection in a mouse dendritic cell line (DC2.4) without cytotoxicity. These results suggest that such pH-responsive unimolecular micelles formed by the well-defined amphiphilic star polymer may serve as promising nano-scale carriers for combined delivery of hydrophobic immunostimulatory drugs (such as imiquimod) and plasmid DNA with potential application in gene-based immunotherapy.

We conduct a systematic comparison of confidence intervals around estimated probabilities of default (PD), using several analytical approaches from large-sample theory and bootstrapped small-sample confidence intervals. We do so for two different PD estimation methods-cohort and duration (intensity)-using twenty-two years of credit ratings data. We find that the bootstrapped intervals for the duration-based estimates are surprisingly tight when compared with the more commonly used (asymptotic) Wald interval. We find that even with these relatively tight confidence intervals, it is impossible to distinguish notch-level PDs for investment grade ratings-for example, a PDAA- from a PDA+. However, once the speculative grade barrier is crossed, we are able to distinguish quite cleanly notch-level estimated default probabilities. Conditioning on the state of the business cycle helps; it is easier to distinguish adjacent PDs in recessions than in expansions.

x, 106p.:ill., The process of teaching in terms ot: for example, use of time requires effective management to ensure quality student achievement. This study sought to investigate how teachers in Kete-Krachi secondary schools manage instructional time. The study used a checklist, a time diary form and an interview guide to collect information from 50 of the targeted teachers, about all activities the teachers engaged in during the entire school week. Data was also obtained about attitude of teachers towards time management. It was found that the teachers engaged in a wide variety of activities, using time that varied from one activity to another; these activities ranged from preparation of lesson notes and sports committee meeting to siesta, preparing cakes for sale and walking home from school; Teachers spent 188.79 minutes, a day, in managing instruction, 146.9 minutes on administrative duties, and a whopping 956.39 minutes on activities encoded social as against 251.64 minutes for instruction. The study also revealed that while some teachers assumed the elevated responsibility of providing instructional leadership for both staff and students, there were others who merely gave instructions without applying any skill necessary for professional practice. If school time management is to improve, teachers would have to find time everyday to think of what to do in advance of actual performance. So it has he en recommended that school administrators proceed with caution when assigning duties to teachers because some duties may have to be run during teaching time.

A rectovaginal pelvimeter, first devised over two decades ago, is reintroduced. By means of this instrument, all of the diameters of the midpelvis can be measured readily and accurately. X-ray pelvimetry can consequently be reduced to only one exposure, and even this one exposure can often be avoided. The hazard of genetic damage from exposure of the gonads to radiation can thus be minimized.

It is usually assumed that the fluctuations of the protein quotient under normal and pathological conditions are due directly or indirectly to variations in the general nature and especially in the rapidity of the metabolic processes. Thus, Cervello (1) ascribes to a retardation of metabolism the rise in globulins he obtained under the administration of antipyrin. Hurwitz and Meyer (2) suppose that the increase in the serum globulins in certain actue infections is due to metabolic disturbances. Schmidt and Schmidt (3) are inclined to believe that the serum proteins have no relation to immunity and would rather attribute the increase in globulins to changes in the metabolism resulting from the toxemia and tissue waste of acute infections. In view of the fact that alterations in the protein quotient have been so frequently attributed by various authors to disturbances in the metabolism, it was considered necessary to investigate the more precise relations of the globulin albumin ratio to difference in the rapidity of metabolism.

Summary A simple and accurate method of measuring the antitryptic indices of blood-sera is described. It is shown that for varying proportions of antitrypsin (= A) added to a specified amount of trypsin (regarded as unity) the relation: holds good for any given serum, T being the proportion of the trypsin neutralized by the serum and C a constant which is a direct measure of the number of molecules of antitrypsin contained in a specified volume of the serum. The molecular concentration of antitrypsin in blood serum is in great excess of the molecular concentration of proteolytically active material in a 1 per cent solution of Gruebler's trypsin.

1. 1. Attention is called to well-known facts which point to the clinical significance of upper midpelvic contractions. 2. 2. Data are presented which show that in contracted pelves the upper midplane is often smaller than the inlet. 3. 3. Evidence is assembled which indicates that the contracted upper midpelvis is an important factor in the etiology of high occipitoposterior arrests, and is a serious obstacle to high midforceps delivery. In a survey of the pelvis, it is therefore necessary to take into consideration the dimensions of the upper midplane as well as the diameters of the inlet and the lower midpelvis. 4. 4. The conclusion is tentatively drawn that cesarean section may often be indicated, even after engagement of the head, in pelves with a contracted inlet in which the upper midplane is smaller than the inlet.

1. 1. Attention is called to the fact that there is a high fetal mortality incident to forceps delivery in funnel pelves. 2. 2. A study of the mechanism of labor in funnel pelves is presented which indicates that the obstruction encountered in forceps delivery is usually due not to preexistent disproportion, but to disproportion resulting from deflexion incident to forceps traction. 3. 3. Deflexion is particularly likely to result in disproportion when there is a coexistent contraction in the sacropubic diameter. 4. 4. The present study substantiates the view long entertained that forceps delivery is usually contraindicated in funnel pelves.

Instrumental procedures of internal pelvimetry are supplemented by Thoms' x-ray method to provide quantitative data for the morphologic classification of pelves. Special emphasis is placed on android characters. The width of the subpubic angle is computed from modified measurements of the anterior sagittal and transverse diameters of the outlet. The bispinous and interischial diameters, and the anterior and posterior sagittal diameters of the narrow pelvic plane, are measured by means of an internal pelvimeter previously described which was especially designed for this purpose. The diameters of the pelvic inlet are determined on a Thoms film. The dimensions measured are the transverse and the anterior and posterior sagittal diameters. The retropubic angle and the degree of curvature of the anterior puboiliac portions are also determined. A morphologic classification of pelves is presented which is based on the classification of Thoms, and of Caldwell and Moloy.

Summary The normal variation in the antitryptic index is very marked in any particular rabbit, and is even greater in different animals. An unmistakable rise in the antitryptic index has been produced in at least two of the six rabbits immunized against trypsin. The progress of immune body production against trypsin is very peculiar, in that at first there is a marked fall in the antitrypsin, followed soon, however, by rather a sudden rise which is at best only 300 per cent above the normal variation. At this level the antibody content remains approximately stationary for a comparatively brief period and is then supervened by a rapid return to the normal, in spite of continued periodical injections of trypsin. Immunity to pancreas trypsin appears to cause no change in the protein quotient. This fact may serve as additional evidence in favor of the recently emphasized view that immunity is non-dependent on the concentration of the serum proteins.

The data presented may be summarized as follows: 1. The anterior midpelvis seems to be of adequate capacity in about one-third of all cases in which the bispinous diameter is narrow. 2. The passage of the largest diameter of the vertex anterior to the ischial spines is probably a common occurrence in pelves with a wide biischial diameter, even when the bispinous diameter is narrow. 3. There is a high incidence of low midpelvic arrest of labor in cases in which the anterior midpelvis is contracted.

Attention is called to the midplane biischial diameter (the diameter between the bases of the ischial spines). A reduction in the width of this diameter to 10.2 cm., or less, is regarded as of clinical significance, with special reference to the narrow upper midpelvis, and high occipitoposterior arrests.