β-Cell Pathophysiology: A Review of Advanced Optical Microscopy Applications

β-cells convert glucose (input) resulting in the controlled release of insulin (output), which in turn has the role to maintain glucose homeostasis. β-cell function is regulated by a complex interplay between the metabolic processing of the input, its transformation into second-messenger signals, and final mobilization of insulin-containing granules towards secretion of the output. Failure at any level in this process marks β-cell dysfunction in diabetes, thus making β-cells obvious potential targets for therapeutic purposes. Addressing quantitatively β-cell (dys)function at the molecular level in living samples requires probing simultaneously the spatial and temporal dimensions at the proper resolution. To this aim, an increasing amount of research efforts are exploiting the potentiality of biophysical techniques. In particular, using excitation light in the visible/infrared range, a number of optical-microscopy-based approaches have been tailored to the study of β-cell-(dys)function at the molecular level, either in label-free mode (i.e., exploiting intrinsic autofluorescence of cells) or by the use of organic/genetically-encoded fluorescent probes. Here, relevant examples from the literature are reviewed and discussed. Based on this, new potential lines of development in the field are drawn.

One- and Two-Slit Experiments with Photons and Electrons: A Proper Resolution

We construct proper microscopic propositions to consistently explain the interference patterns obtained for electrons and photons in well-defined one- and two-slit experiments. Our propositions are also made explicit on the basis of quantum mechanics with proper quantitative analysis to support the correctness of the physical mechanisms proposed herein, which obey the wave-particle duality. Apart from that, the microscopic propositions constructed herein can be treated as guidelines in setting up the future experiments such that one can unambiguously support or oppose this strange notion—a quantum particle behaves differently depending upon the number of slit, and where we place the detector such that the particle can sense the detector and the number of slit, before physically interacting with them.

The Path to Effective Governance of “X” Village from the Perspective of Rural Revitalization

Rural governance is described as a continuous improvement of internal self-management in rural areas as well as the proper resolution of rural development issues. This article believes that effective rural governance must be achieved. Persist in the initial combination of autonomy, the legal system and the “three governance” system of the rule of virtue, and promote the complete and effective advancement of the rural social governance system. Continuously improve the level of spiritual civilization in rural areas through effective rural governance, and strive to promote rural revitalization.

Fuzzy Image Processing Based Architecture for Contrast Enhancement in Diabetic Retinopathy Images

Diabetic retinopathy” is damage to retina denotes one of the problems of diabetes which is a significant reason for visual infirmity and blindness. A comprehensive and routine eye check is important to early detection and rapid treatment. This study proposes a hardware system that can enhance the contrast in the diabetic retinopathy eye fundus images as a first step in different eye disease diagnoses. The fuzzy histogram equalization technique is proposed to increases the local contrast of Diabetic Retinopathy Images. First, a histogram construction hardware architecture for different image processing purposes has been built then modified with fuzzy techniques to create fuzzy histogram equalization architecture, which is used to enhance the original images. Both architectures are designed using a finite-state machine (FSM) technique and programmed with VHDL programming language. The first one is implemented using two (Spartan 3E-XC3S500 and Xilinx Artix-7 XC7A100T) kits, while the second architecture is implemented using (Spartan 3E-XC3S500) kit. The system consists also of a modified video graphics array (VGA) port to display the input and resulted images with a proper resolution. All the hardware outputs are compared to that results produce from MatLab for verification and the resulted images are tested by PSNR, MSE, ENTROPY ,and AMBE

The Mutuality of National and International Identities in International Sports Law

The network of institutions that comprise the Olympic Movement include several whose authoritative scope now extends far beyond the mere staging of the Olympic and Paralympic Games to govern some important aspects of virtually all major regional and global competition and to foster the development of a comprehensive body of international sports law. The issues include nationality, which is the focus of this essay. More broadly, the proper resolution of nationality issues in the sports arena offers a limited model for reconciling tensions between national and international interests in the progressive development of international law.

A gatekeeping function of the replicative polymerase controls pathway choice in the resolution of lesion-stalled replisomes

DNA lesions stall the replisome and proper resolution of these obstructions is critical for genome stability. Replisomes can directly replicate past a lesion by error-prone translesion synthesis. Alternatively, replisomes can reprime DNA synthesis downstream of the lesion, creating a single-stranded DNA gap that is repaired primarily in an error-free, homology-directed manner. Here we demonstrate how structural changes within theEscherichia colireplisome determine the resolution pathway of lesion-stalled replisomes. This pathway selection is controlled by a dynamic interaction between the proofreading subunit of the replicative polymerase and the processivity clamp, which sets a kinetic barrier to restrict access of translesion synthesis (TLS) polymerases to the primer/template junction. Failure of TLS polymerases to overcome this barrier leads to repriming, which competes kinetically with TLS. Our results demonstrate that independent of its exonuclease activity, the proofreading subunit of the replisome acts as a gatekeeper and influences replication fidelity during the resolution of lesion-stalled replisomes.

Professor Anastas Kocarev, First Macedonian Oncologist with Worldwide Reputation and Pioneer in Cancer Diagnostics and Treatment with Radium

PhD. Anastas Kocarev (Kotzareff in French) is one of the most prominent Macedonian doctors and experts, prolific contributor to the cancer research in Switzerland and France in the first decades of the 20th century. He was born in Ohrid on May 5th, 1889. He graduated from the Faculty of Medicine in Geneva where he defended a doctorate in medicine in 1915. In 1916 he was elected Assistant Professor (Private Docent) at that Faculty. He was a prominent scientist and professor of experimental medicine at the Faculty of Medicine in Geneva and the Sorbonne University in Paris, with a wide reputation in Europe and the United States. PhD. A. Kocarev is one of the pioneers of oncology and radiology in the world, a forerunner of modern nuclear medicine and positron emission tomography. He was a close associate of Nobel laureate in chemistry and physics Maria Sklodovska-Curie and at her invitation moved to Paris in 1925 to continue the research on the diagnosis and treatment of cancer using radium. He was fully devoted to science and published numerous scientific papers and books with high citations and dissemination in many medical libraries in Europe and beyond. In addition to his professional teaching and scientific work as a top oncologist-radiologist, he was a great patriot with advanced political ideas. He founded the Academic Society “Macedonia” in Geneva, in 1915, and united it with other Macedonian political associations from Zurich and Lausanne, in 1918, into a joint “Alliance of Macedonian Societies for Independent Macedonia”, with commitments, activities and initiatives to the Society of Nations, based in Geneva, Switzerland, for the proper resolution of the Macedonian national issue by creating a united and independent state “Macedonia” or the formation of a “Balkan Federation”. He died suddenly in Paris on March 29, 1931.

Spiritual Song in Ukrainian Folklore Milieu

The paper outlines the original phenomenon of a spiritual song in the Ukrainian oral tradition, determines characteristic features of these texts and their functions. Besides, the author focuses on some special research issues concerning the folklore religious repertoire, first of all, the specificity of the relationship between spiritual and secular epic songs. The spiritual song in the Ukrainian oral tradition is a large group of poetical and musical works, united primarily by the religious Christian themes and endowed with the ability to acquire special spiritual meaning in the life of a believer, exercise an important function of satisfying his/her spiritual religious needs. Another defining feature of these songs is a lack of clear attachment to a certain rite, time, occasion. An episodic attachment of individual texts to the rite only reveals their multifunctionality, since, as a rule, the same work may be used in various rituals, appear in the repertoire of professional singers, and perform some other functions simultaneously. Essential for the differentiation of the spiritual song phenomenon in the folklore milieu is the fact of distinguishing this group of works and perceiving it as integrity by the bearers of tradition themselves until now. They use special folk concepts for its designation (‘God’s songs’, ‘psalms’). At the same time, this large stratum of folk repertoire is divided into two sub-groups, namely folklorized songs of book origin and those of folk origin. Thus, the phenomenon of a spiritual song in the Ukrainian oral tradition is characterized by a rich variety of texts in terms of character, time of emergence, nature, form, style, and genre features. The practice of perception, recording, and comprehension of spiritual songs has developed certain concepts and approaches. The present paper offers an attempt to systematize the previous experience and distinguish the problems that were raised in the works by various researchers and remained topical, often lacking a proper resolution. Attention to the system of the research approaches gives a guideline to the author and forms a sense of the continuing tradition.

A gatekeeping function of the replicative polymerase controls pathway choice in the resolution of lesion-stalled replisomes

DNA lesions stall the replisome and proper resolution of these obstructions is critical for genome stability. Replisomes can directly replicate past a lesion by error-prone translesion synthesis. Alternatively, replisomes can reprime DNA synthesis downstream of the lesion, creating a single-stranded DNA gap that is repaired primarily in an error-free, homology-directed manner. Here we demonstrate how structural changes within the bacterial replisome determine the resolution pathway of lesion-stalled replisomes. This pathway selection is controlled by a dynamic interaction between the proofreading subunit of the replicative polymerase and the processivity clamp, which sets a kinetic barrier to restrict access of TLS polymerases to the primer/template junction. Failure of TLS polymerases to overcome this barrier leads to repriming, which competes kinetically with TLS. Our results demonstrate that independent of its exonuclease activity, the proofreading subunit of the replisome acts as a gatekeeper and influences replication fidelity during the resolution of lesion-stalled replisomes.

RP-HPLC AND HPTLC METHOD DEVELOPMENT AND VALIDATION FOR ESTIMATION OF DOLUTEGRAVIR IN BULK AND TABLET DOSAGE FORM

Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (INSTI), antiretroviral drug. RP-HPLC and HPTLC methods have been developed and validated for DTG in bulk and tablet dosage form. In HPLC method, analysis was carried out on C-18 column using a mixture of acetonitrile: phosphate buffer (pH 7.0) in the ratio of (90:10 V/V) as mobile phase at the flow rate 1 mL/min at 261 nm. The method was found to be linear in the concentration range 10-70 μg/mL. Peak for DTG was observed at 2.8 ± 0.1 minutes. For HPTLC method proper resolution was achieved with toluene: methanol: formic acid 7:3:0.1(V/V/V) as the mobile phase at 334 nm. HPTLC method was found to be linear in concentration range of 200-600 ng/band. Rf value of DTG was found to be 0.496 ± 0.0055. Developed methods were validated as per ICH guidelines Q2(R1) and were found to be accurate, precise, simple and robust.