33 research outputs found
Study of stimuli-responsive degradation using a disulfide platform in different polymeric biomaterials
Polymers have great potential as building blocks to construct biomaterials for applications in biomedicine, pharmaceutics and biotechnology. Their chemical flexibility leads to the synthesis of materials with diverse physical and mechanical properties. Specifically, stimuli-responsive polymers are engineered to undergo chemical or physical transitions in response to specific external triggers. One such response involves the cleavage or degradation of a dynamic covalent bond within the polymer structure. Particularly, the reduction of disulfide bonds has gained significant attention in the development of complex delivery systems for therapeutics. This thesis describes the development of two different reduction-responsive biomaterials.
Amphiphilic block copolymers (ABPs) self-assemble in aqueous solutions to form core/shell micelles consisting of a hydrophobic core, capable of carrying a variety of hydrophobic therapeutic agents, and a hydrophilic corona, able to improve circulation time and delay immune responses. This unique property, in addition to enhanced colloidal stability and tunable size with narrow size distribution, makes micelles promising candidates for drug delivery systems. Hence, a polyester-based reduction-responsive degradable ABP with disulfide linkages positioned repeatedly on the main chain at regular intervals is synthesized. These well-defined ABPs were synthesized by a combination of polycondensation and atom transfer radical polymerization (ATRP). These ABPs self-assemble in aqueous solution, resulting in spherical micelles with a monomodal distribution. In the presence of a reducing agent, disulfide bonds are cleaved, leading to a destabilization of the micellar core and thus enhanced release of encapsulated model drugs. Demonstrating the potential drug delivery applications of polymeric micellar systems, functionalization with biotin (vitamin H) leads to bioconjugated micelles capable of potential cell-targeting.
Hydrogels are three-dimensional networks of hydrophilic polymers that have shown promise as tissue engineering scaffolds. Thermo-responsive hydrogels expel water above their lower critical solution temperature (LCST), becoming more hydrophobic, and hence lose volume. Hydrogels were synthesized by ATRP using biocompatible oligo(ethylene oxide) as a scaffolding material in the presence of a disulfide-labeled dimethacrylate cross-linker. The amount of cross-linker affects thermo-responsive and mechanical properties. Cleavage of disulfide bonds lead to an increased LCST, enhanced deswelling kinetics and a decrease in mechanical properties caused by the generation of hydrophilic dangling chains, increasing the overall hydrophilicity of hydrogels. Combined with these results, as well as enhanced release of encapsulated hydrophilic model drugs and non-toxicity, these hydrogels show promise for biomedical applications
Analyzing power in elastic scattering of the electrons off a spin-0 target
We consider the analyzing power on a spin-0 nuclear target. This observable
is related to the imaginary part of the two-photon-exchange (box) diagram. We
consider the contributions of elastic and inelastic intermediate states. The
former requires knowledge of the elastic nuclear form factor, while the latter
uses the optical theorem as input. The elastic contribution scales as the
nuclear charge , while the inelastic contribution as the ratio of the atomic
number and nuclear charge, . We provide estimates for He and
Pb, in the kinematics of existing or upcoming experiments. In both
cases, we predict negative values of a few parts per million, and the dominant
contribution is due to inelastic contributions. The analyzing power can
contribute a substantial systematic error in parity-violating experiments.Comment: 6 pages, 8 figure, one table; submitted to Phys.Rev.C; one figure
corrrecte
Improvement of the algorithm for diagnostics of postcholecystectomy syndrome taking into account functional and organic changes in the area of the large duodenal nipple
The aim. Improving the algorithm for diagnosing patients with postcholecystectomy syndrome (PCS), taking into account functional and organic changes in the major duodenal papilla (MDP).
Materials and methods. 208 patients with PCS were examined. Laparoscopic cholecystectomy (CE) was performed in 172 patients in history, open CE was performed in 36 patients. 47 patients had obstructive jaundice, 84 had signs of biliary hypertension without an increase in bilirubin, 77 had no signs of biliary hypertension and an increase in bilirubin.
The following instrumental research methods were used: abdominal organs ultrasound examination (AO USE), duodenoscopy, endoscopic retrograde cholangiopancreatography (ERCP), computed tomography (CT). In the main group, to study the morphofunctional changes in MDP, duodenoscopy with parietal impedancemetry, ultrasound of the hepatobiliary zone with a choleretic load were used.
Results. In the main group, 34 patients underwent ultrasound of the hepatobiliary zone and Vater's nipple area with a choleretic breakfast according to Boyden according to the method of Grigoriev P.Ya. in our modification, 21 patients had an expansion of the choledochus by 2 mm. At the same time, taking meverin led to a decrease in the diameter of the choledochus, which indicated functional changes in the MDP. In 13 patients, the expansion of the choledochus, observed when taking a choleretic breakfast, persisted with the use of antispasmodics, which indicated the presence of an organic pathology of MDP. Duodenoscopy with impedancemetry was performed in 41 patients: 20 patients had 760–820 Ohm, which indicated the presence of functional changes, 12 patients had inflammatory changes in the MDP and 703–760 Ohm were detected, 9 patients with cicatricial fibrous changes had indicators impedance measurement 640–703 Ohm. The use of ultrasound with a choleretic breakfast and duodenoscopy with parietal impedancemetry in patients of the main group made it possible to identify functional and organic (inflammatory, fibrous) changes in the MDP, which made it possible to develop a therapeutic algorithm using both conservative therapy and the use of various options for transpapillary endoscopic interventions.
Conclusions. Conducting an in-depth diagnosis of morpho-functional changes in MDP using parietal impedancemetry of MDP and ultrasound of the hepatobiliary zone with choleretic load allows us to identify both functional and morphological changes in MDP, which makes it possible to develop a therapeutic algorithm using drug therapy and transpapillary endoscopic techniques.The aim. Improving the algorithm for diagnosing patients with postcholecystectomy syndrome (PCS), taking into account functional and organic changes in the major duodenal papilla (MDP).
Materials and methods. 208 patients with PCS were examined. Laparoscopic cholecystectomy (CE) was performed in 172 patients in history, open CE was performed in 36 patients. 47 patients had obstructive jaundice, 84 had signs of biliary hypertension without an increase in bilirubin, 77 had no signs of biliary hypertension and an increase in bilirubin.
The following instrumental research methods were used: abdominal organs ultrasound examination (AO USE), duodenoscopy, endoscopic retrograde cholangiopancreatography (ERCP), computed tomography (CT). In the main group, to study the morphofunctional changes in MDP, duodenoscopy with parietal impedancemetry, ultrasound of the hepatobiliary zone with a choleretic load were used.
Results. In the main group, 34 patients underwent ultrasound of the hepatobiliary zone and Vater's nipple area with a choleretic breakfast according to Boyden according to the method of Grigoriev P.Ya. in our modification, 21 patients had an expansion of the choledochus by 2 mm. At the same time, taking meverin led to a decrease in the diameter of the choledochus, which indicated functional changes in the MDP. In 13 patients, the expansion of the choledochus, observed when taking a choleretic breakfast, persisted with the use of antispasmodics, which indicated the presence of an organic pathology of MDP. Duodenoscopy with impedancemetry was performed in 41 patients: 20 patients had 760–820 Ohm, which indicated the presence of functional changes, 12 patients had inflammatory changes in the MDP and 703–760 Ohm were detected, 9 patients with cicatricial fibrous changes had indicators impedance measurement 640–703 Ohm. The use of ultrasound with a choleretic breakfast and duodenoscopy with parietal impedancemetry in patients of the main group made it possible to identify functional and organic (inflammatory, fibrous) changes in the MDP, which made it possible to develop a therapeutic algorithm using both conservative therapy and the use of various options for transpapillary endoscopic interventions.
Conclusions. Conducting an in-depth diagnosis of morpho-functional changes in MDP using parietal impedancemetry of MDP and ultrasound of the hepatobiliary zone with choleretic load allows us to identify both functional and morphological changes in MDP, which makes it possible to develop a therapeutic algorithm using drug therapy and transpapillary endoscopic techniques
Model-dependence of the dispersion correction to the parity-violating asymmetry in elastic scattering
We analyze the dispersion correction to elastic parity violating
electron-proton scattering due to exchange. In particular, we
explore the theoretical uncertainties associated with modeling contributions of
hadronic intermediate states. Taking into account constraints from low- and
high-energy, parity-conserving electroproduction measurements, choosing
different models for contributions from the non-resonant processes, and
performing the corresponding flavor rotations to obtain the electroweak
amplitude, we arrive at an estimate of the uncertainty in the total
contribution to the parity-violating asymmetry. At the kinematics of the Q-Weak
experiment, we obtain a correction to the asymmetry equivalent to a shift in
the proton weak charge of . This should be compared to the
value of the proton's weak charge of \qwp=0.0713\pm0.0008 that includes SM
contributions at tree level and one-loop radiative corrections. Therefore, we
obtain a new Standard Model prediction for the parity-violating asymmetry in
the kinematics of the Q-Weak experiment of . The latter error leads to a relative uncertainty of 2.8% in the
determination of the proton's weak charge, and is dominated by the uncertainty
in the isospin structure of the inclusive cross section. We argue that future
parity-violating inelastic asymmetry measurements at low-to-moderate
and could be exploited to reduce the uncertainty associated with the
dispersion correction. Because the corresponding shift and error bar decrease
monotonically with decreasing beam energy, a determination of the proton's weak
charge with a lower-energy experiment or measurements of "isotope ratios" in
atomic parity-violation could provide a useful cross check on any implications
for physics beyond the Standard Model derived from the Q-Weak measurement.Comment: 25 pages, 17 figures, 4 tables; revised version accepted for
publication in PR
Reductively degradable polyester-based block copolymers prepared by facile polycondensation and ATRP: synthesis, degradation, and aqueous micellization
Well-defined reductively degradable amphiphilic block copolymers having disulfide linkages positioned repeatedly on hydrophobic chains, thus exhibiting fast degradation, were prepared by a combination of polycondensation and ATRP. The new method consists of three synthetic steps including, (1) polycondensation of commercially available diols and diacids through carbodiimide coupling or high temperature processes to synthesize degradable polyesters with disulfides labeled on the main chain at regular intervals (ssPES–OH), (2) bromination of ssPES–OH to ssPES–Br, and (3) ATRP for chain extension of ssPES–Br with water-soluble polymethacrylate, yielding ssPES-b-polymethacrylate block copolymers (ssABPs). The reductive cleavage of disulfide linkages in reducing conditions resulted in the degradation of ssPES homopolymers; their degradation rate was significantly enhanced with the increasing amounts of disulfide linkages in ssPES–OH and reducing agents. For ATRP, gel permeation chromatography and 1H-NMR results confirmed the synthesis of well-defined ssABPs and revealed that polymerizations were well controlled. Because of their amphiphilic nature, ssABPs self-assembled in water toward the formation of core/shell micelles consisting of a hydrophobic ssPES core surrounded with polymethacrylate coronas. The effects of the corona's chain length on thermal properties and micellization in water of well-defined ssABPs were examined. Moreover, reductive (or thiol-responsive) degradation of ssABP-based micelles enabled fast release of encapsulated model drugs. Cell culture experiments confirmed nontoxicity and biocompatibility of well-defined ssABPs as effect candidates for targeted delivery applications
Glutathione-triggered disassembly of isothermally responsive polymer nanoparticles obtained by nanoprecipitation of hydrophilic polymers
The encapsulation and selective delivery of therapeutic compounds within polymeric nanoparticles offers hope for the treatment of a variety of diseases. Traditional approaches to trigger selective cargo release typically rely on polymer degradation which is not always sensitive to the biological location of a material. In this report, we prepare nanoparticles from thermoresponsive polymers with a ‘solubility release catch’ at the chain-end. This release catch is exclusively activated in the presence of intracellular glutathione, triggering an ‘isothermal’ response and promoting a change in polymer solubility. This solubility switch leads to specific and rapid nanoparticle disassembly, release of encapsulated cargo and produces completely soluble polymeric side-products
Dispersion of watermelon rinds as secondary raw materials in technologies of pectin-containing extracts and film structures
The development of protective coatings based on pectin substances that serve as natural structure-forming agents developed from a secondary resource base is focused on removing a complex problem in the production of finished products by deep processing of basic raw materials and developing an original film material. At the same time, the technical result of obtaining pectin-containing film structures is their ability to protect food products from microbiological spoilage, natural losses during storage and the preservation of quality and safety indicators. An important preparatory procedure that determines the efficiency and intensity of extraction processes can be attributed to the operation of dispersing the feedstock, since it directly affects the size of the contact surface area of the phases involved in mass transfer. However, it is clear that the greater the degree of grinding, the higher the efficiency of the process, but an excessive increase can lead to additional unjustified energy costs and, as a result, to an increase in the cost of the finished products sold. In this regard, the purpose of the research is to analyze existing technologies for producing pectin-containing extracts, in which watermelon rinds can be used as secondary resources and to intensify the extraction process by conducting a rational preparatory procedure for grinding the raw materials. The object of the research are watermelon rinds as non-recyclable waste from processing watermelon raw materials. According to the obtained graphs, and taking into account the high rates of gelatinization of the obtained pectin extracts, it is possible to recommend a complex treatment of watermelon rinds, including, in addition to the operations of preliminary preparation of raw materials, ultrasonic exposure and acid hydrolysis, and it is desirable to use food acids, for example, acetic or citric, instead of aggressive sulfuric and hydrochloric acids. As a result of the study of the dispersed composition, it has been concluded that the average equivalent particle size of the dispersed raw materials does not exceed the recommended limits, that is, the result obtained can be considered acceptable
Review of two-photon exchange in electron scattering
We review the role of two-photon exchange (TPE) in electron-hadron
scattering, focusing in particular on hadronic frameworks suitable for
describing the low and moderate Q^2 region relevant to most experimental
studies. We discuss the effects of TPE on the extraction of nucleon form
factors and their role in the resolution of the proton electric to magnetic
form factor ratio puzzle. The implications of TPE on various other observables,
including neutron form factors, electroproduction of resonances and pions, and
nuclear form factors, are summarized. Measurements seeking to directly identify
TPE effects, such as through the angular dependence of polarization
measurements, nonlinear epsilon contributions to the cross sections, and via e+
p to e- p cross section ratios, are also outlined. In the weak sector, we
describe the role of TPE and gamma-Z interference in parity-violating electron
scattering, and assess their impact on the extraction of the strange form
factors of the nucleon and the weak charge of the proton.Comment: 73 pages, 40 figures, review article for Prog. Part. Nucl. Phys.
(dedicated to the memory of John A. Tjon
Recommended from our members
The Violation of Democracy: Unequal Access to the Shaping of Government
The United States government was built to protect against a tyrannical government in which the wishes of the minority elite are prioritized ahead of the wishes of the majority. The fear of such minority influence in government is now grounded in the rise of wealthy corporations. With the rise of corporations, the United States has become increasingly economically dependent on major companies. Corporations are uniquely positioned economically to bargain for political advantage, and political campaigns are especially vulnerable to this relationship due to their heavy reliance on donors. Consequently, campaign finance laws have been established with the goal of curtailing corporate political influence. Campaign finance laws have undergone several interpretations by the highest court in the United States to address evolving public concerns surrounding corruption. Most notable is the 1975 Buckley v. Valeo case, where the Supreme Court ruled that the wealthy minority not be given free rein to deposit funds toward their favorite candidates, citing corruption and the appearance of corruption as justification. From this, one can derive the appearance of corruption to mean any outcome by which public trust in the American democratic system is justly diminished. However, dissenters opined that despite governmental interest against corruption, the Court’s remedy was overinclusive and thus violated First Amendment protections to political speech. The twenty-first century rulings of Citizens United v. Federal Election Commission and McCutcheon v. Federal Election Commission overturned precedent and opened a floodgate of money that can now participate in politics, birthing an over 3.5 billion dollar lobbying industry by which a direct line of communication between large companies and legislative leaders was granted. Such a connection between the two powers has constructed a dangerous relationship between Big Money and political mobility. The goal of this paper is to understand how the rulings in Citizens United and McCutcheon changed the extent to which ordinary persons can access and shape government. This paper understands the shaping of government to mean any means by which an individual or group of individuals influence policymakers; unequal access to the shaping of government then refers to any circumstance under which a minority possesses a disproportionate influence over a policymaker’s attention compared to ordinary persons. To accomplish its goal, this paper will study the relevant facts of the two cases, assess the arguments through which the Court’s decisions were made, and gauge the possible outcomes of the Court’s decisions