Investigating factor interactions in formalising the process of developing new products

The creation of new product development programmes in industrial organisations, as a process involves a system of activities for defining, planning and implementing projects, with a view to successful market realisation. The success of a programme and its associated projects is not unambiguous (depends to some extent on the participants' point of view) and can be related to the achievement of predetermined goals and constraints, customer satisfaction, organisational knowledge, etc. For the respective industrial company, the planning process is more important than the plan itself, because hypotheses are checked; comparable alternatives are analysed; the future consequences of one or another of today's decisions are investigated; the necessary changes to the prerequisites are made.The survey was conducted in 560 medium and large enterprises operating in the manufacturing industry of Bulgaria. The aim is to establish independent factor variables and their value impacts on the effective management of the process of developing new products related to the dependent variable "formalisation or use of officially documented procedures describing the new product development (NPD) process".In order to meet the target, a quantitative study was carried out by applying a correlation and regression analysis to search for relationships and dependences between the variables examined. A regression model is presented for the dependent variable studied. The results and recommendations obtained can be used to improve the management of the product innovation process

Dissemination of anthrax in humans in stationary anthrax outbreaks in Dobrudzha region

Болестта антракс е зооноза, която се разпространява главно от трупове на заразени и умрели домашни и диви животни. По хората се разпространява чрез контакт със заразени животни, заразена почва, месо и предмети, имали досег с трупа.Цел: Да проучим зависимостта между природо-географските условия на почвите и разпространението на антракса при хората за периода 1991-2013 година в област Добрич.Материали: Данните от официалната регистрация на заразните заболявания в Добрич и страната.Методи: Частичен епидемиологичен анализ, картографски методи, статистически методи.Резултати: Специфичното разпростране ние на антракса зависи от степента на развито животновъдство в даден район и от характера на почвите, в които попадат спорите. За съществуването и оцеляването на бацила в почвата влияние оказват не толкова температурата и влажността, a по-скоро наличието на органични съединения, които да служат за микроба като благоприятен субстрат.Изводи: Черноземните почви в Добруджанския край, с натрупването на хумус в значителни количества, слабо алкални или неутрални и с много други органични вещества са подходящи за дългогодишното съхранение на инвазиоспособни спори, включително и антраксни. Заболяванията от антракс при хората в област Добрич са регистрирани в 9 години, от проучвания 23-годишен период, в 5 общини, със засегнати 11 населени места.Anthrax is a zoonotic disease, which is spread mainly by carcasses of infected and dead domestic and wild animals. In people it is spread by contact with infected animals, contaminated soil, meat and objects which were in contact with the body.Aim: To investigate the relationship between geographic conditions of the soil and the spread of anthrax in humans for the period 1991-2013 year in the Dobrich region.Materials: We have used data from the official registration of communicable diseases in the Dobrich region and in the country.Methods: We have used partial epidemiological analysis, cartographic methods, statistical methods. Results: The specific distribution of anthrax depends on the extent of livestock farming in a given area and the nature of the soils, where spores fall. The existence and survival of the bacillus in the soil is influenced not so much by the temperature and humidity, but rather by the presence of organic compounds that serve as favorable microbial substrate.Conclusions: Black soil in the Dobrudzha region, with the accumulation of humus in significant quantities, being slightly alkaline or neutral and containing many other organic substances are suitable for longterm storage of invasive spores, including anthrax. Anthrax in humans in Dobrich were registered in nine years, from the studied 23-year period in 5 municipalities, with 11 affected settlements

Interferon-γ Receptor Signaling in Dendritic Cells Restrains Spontaneous Proliferation of CD4+ T Cells in Chronic Lymphopenic Mice

In lymphopenic mice, T cells become activated and undergo lymphopenia-induced proliferation (LIP). However, not all T cells are equally sensitive to lymphopenia. Several lymphopenia-insensitive T cell clones were described and their non-responsiveness was mainly attributed to clone-specific properties. Here, we provide evidence for an additional, host-dependent mechanism restraining LIP of lymphopenia-insensitive CD4+ T cells. We show that such cells undergo LIP in lymphopenic mice lacking IFN-γ receptor (IFN-γR) expression, a process, which is promoted by the autocrine action of T cell-derived IFN-γ. Additionally, LIP of lymphopenia-insensitive CD4+ T cells requires an intact microflora and is accompanied by the massive accumulation of IL-6 and dendritic cells (DCs). Consistent with these results, IL-6 neutralization and the DC-specific restoration of IFN-γR expression are both sufficient to restrict LIP. Hence, the insensitivity of CD4+ T cells to lymphopenia relies on cell-intrinsic properties and a complex interplay between the commensal microflora, IL-6, IFN-γR+ DCs, and T cell-derived IFN-γ

Engineering T-cell Activation for Immunotherapy by Mechanical Forces

Adoptive immunotherapy relies on the isolation, modification, activation, and transfer of antigen-specific T-cells. With constant advances in bioengineering, each individual step in T-cell activation and expansion can be further improved. In this review, we discuss the current knowledge on factors influencing the mechanical forces applied on a T-cell during activation. We provide insights from ligand presentation and surface modification and present ideas of a mechanobiological signal transduction from extracellular receptor–ligand interaction to intranuclear gene expression changes as a determining factor of a T-cell response

Investigation of Hydrogen Storage Characteristics of MgH2 Based Materials with Addition of Ni and Activated Carbon

Magnesium-based materials are promising as hydrogen storage media due to their high theoretical hydrogen absorption capacity, abundance and low price. The subject of this study are the hydrogen sorption characteristics of the composites 80 wt % MgH2-15 wt % Ni-5 wt % activated carbon (synthesized from polyolefin wax, a waste product of polyethylene production at low pressure which will be denoted further in the text as POW) and 90 wt % MgH2-5 wt % Ni-5 wt % POW, prepared by ball milling under argon atmosphere. Structure, phase and surface composition of the samples before and after hydrogenation are determined by XRD and TEM. The maximum absorption capacity value of the composites at a temperature 573 K and after 60 min. of hydrogenation are 5.3 wt % H2 for the material with higher Ni content and 5.5 wt % H2 for the other sample. The presence of both additives—nickel and activated carbon derived from POW—has a positive impact on hydrogenation kinetics and the capacity achieved. The results from TEM characterization, e.g., the polycrystalline SAED (selected area electron diffraction) show the presence of graphite, Mg and monoclinic Mg2NiH4

External cues to drive B cell function towards immunotherapy

Immunotherapy stands out as a powerful and promising therapeutic strategy in the treatment of cancer, infections, and autoimmune diseases. Adoptive immune therapies are usually centered on modified T cells and their specific expansion towards antigen-specific T cells against cancer and other diseases. However, despite their unmatched features, the potential of B cells in immunotherapy is just beginning to be explored. The main role of B cells in the immune response is to secrete antigen-specific antibodies and provide long-term protection against foreign pathogens. They further function as antigen-presenting cells (APCs) and secrete pro- and anti-inflammatory cytokines and thus exert positive and negative regulatory stimuli on other cells involved in the immune response such as T cells. Therefore, while hyperactivation of B cells can cause autoimmunity, their dysfunctions lead to severe immunodeficiencies. Only suitably activated B cells can play an active role in the treatment of cancers, infections, and autoimmune diseases. As a result, studies have focused on B cell-targeted immunotherapies in recent years. For this, the development, functions, interactions with the microenvironment, and clinical importance of B cells should be well understood. In this review, we summarize the main events during B cell activation. From the viewpoint of mechanobiology we discuss the translation of external cues such as surface topology, substrate stiffness, and biochemical signaling into B cell functions. We further dive into current B cell-targeted therapy strategies and their clinical applications. © 2021 Elsevier Ltd.ISSN:1742-7061ISSN:1878-756

Non-neutralizing antibodies protect against chronic LCMV infection by promoting infection of inflammatory monocytes in mice

Antibodies play an important role in host defense against microorganisms. Besides direct microbicidal activities, antibodies can also provide indirect protection via crosstalk to constituents of the adaptive immune system. Similar to many human chronic viral infections, persistence of Lymphocytic choriomeningitis virus (LCMV) is associated with compromised T- and B-cell responses. The administration of virus-specific non-neutralizing antibodies (nnAbs) prior to LCMV infection protects against the establishment of chronic infection. Here, we show that LCMV-specific nnAbs bind preferentially Ly6Chi inflammatory monocytes (IMs), promote their infection in an Fc-receptor independent way, and support acquisition of APC properties. By constituting additional T-cell priming opportunities, IMs promote early activation of virus-specific CD8 T cells, eventually tipping the balance between T-cell exhaustion and effector cell differentiation, preventing establishment of viral persistence without causing lethal immunopathology. These results document a beneficial role of IMs in avoiding T-cell exhaustion and an Fc-receptor independent protective mechanism provided by LCMV-specific nnAbs against the establishment of chronic infection.ISSN:0014-2980ISSN:1521-414

Clinical significance and change in the degree of mitral insufficiency after TAVI

Въведение: Хемодинамично значима митралната инсуфициенция (МиИ) се среща при до 20-30 % от пациентите с високостепенна аортната стеноза (АС), показани за транскатетърна аортна клапна имплантация (ТАVI). Въпреки утвърждаването на метода като стандарт при лечение на високорискови за хирургия пациенти в световен мащаб и все по-големият брой пациенти лекувани интервенционално, поведението при съпътстваща значима МиИ продължава да бъде диагностично и терапевтично предизвикателство. Решението за намеса върху множество клапи трябва да вземе предвид допълнителния хирургичен риск при комбинираните процедури. Значимата МиИ е свързана с по-лоша прогноза както при хирургично, така и при интервенционално лечение. При висок оперативен риск и при значима МиИ, ТАVI е възможно решение поради доказаното намаляване на тежестта при значителна част от пациентите. Цел на тази статия е да оцени влиянието на значимата вторична МиИ върху смътрността и промяната на степентта и след ТАVI. Материал и методи: Статията представлява ретроспективен анализ на 50 пациента с високостепенна симптоматична аортна стеноза, при които е извършена успешна ТАVI. Пациентите са проследени за период от 1 година и са разделени в две големи групи – без значима МR (0,1 степен) и такива със значима вторична МиИ (≥ 2 степен). Проследени са общата смъртност, сърдечносъдова смъртност, функционален клас сърдечна недостатъчност по класификацията NYHA, фракция на изтласкване и необходимост от рехоспитализации. Изводи: Хемодинамично значимата вторична МиИ, съпътстваща високостепенна АС преди TAVI претърпява положителна динамика при значителна част от пациентите постпроцедурно и трябва да се има предвид при вземането на решение за терапевтичната стратегия от Heart team. Влошаването на значимата вторична МиИ при изследваните пациенти е свързано с 30-дневна и едногодишна сърдечно-съдова смъртност и необходимост от рехоспитализации, което е в съответствие с данни, че значение за прогнозата има не само наличието на значима вторична МиИ, а нейната динамика след TAVI. Introduction: Hemodynamically signifi cant mitral regurgitation (MR) occurs in up to 20-30% of patients with high-grade aortic stenosis (AC) indicated for transcatheter aortic valve implantation (TAVI). Despite the establishment of the method as a standard in the treatment of high-risk patients for surgery worldwide and the growing number of patients treated interventionally, behavior in concomitant signifi cant MR continues to be a diagnostic and therapeutic challenge. The decision to intervene on multiple valves must take into account the additional surgical risk of the combined procedures. Signifi cant MR is associated with a worse prognosis in both surgical and interventional treatment. With high operative risk and signifi cant MR, TAVI is a possible solution due to the proven reduction in severity in a signifi cant proportion of patients. The aim of this paper is to evaluate the impact of signifi cant secondary MR on mortality and rate change after TAVI. Material and methods: The article is a retrospective analysis of 50 patients with high-grade symptomatic aortic stenosis who underwent successful TAVI. Patients were followed for a period of 1 year and were divided into two major groups – no signifi cant MR (0.1 degree) and those with signifi cant secondary MR (≥ grade 2). Overall mortality, cardiovascular mortality, functional class of heart failure according to the NYHA classifi cation, ejection fraction and need for rehospitalizations weremonitored. Conclusions: Hemodynamically signifi cant secondary MR, concomitant high-grade AC before TAVI undergoes positive dynamics in a signifi cant proportion of patients postprocedurally and should be considered when deciding on a therapeutic strategy by the Heart team. The worsening of signifi cant secondary MI in the studied patients is associated with 30-day and one-year cardiovascular mortality and the need for rehospitalization, which is consistent with data that the prognosis is important not only the presence of signifi cant secondary MR, but its dynamics after TAVI

The combination of rIL-7 therapy and peptide vaccination impairs T cell-dependent tumor rejection in Rag^-/- mice.

<p>(A) Rag^-/- and (B) Rag^-/-IL-7R^-/- mice were reconstituted with 1 x 10⁶ CD8⁺CD90.1⁺ OT-I T cells or were left untreated (+/- OT-I). One day later, OT-I-reconstituted mice were either vaccinated with 50 μg SIINFEKL or received PBS (+/- Pep). rIL-7 or PBS (+/- IL-7) were injected every 3–4 days for 19 days starting one day before T cell transfer. Mice were challenged s.c. with 1 x 10⁶ EG7 tumor cells three weeks after T cell transfer. Mice with tumors larger than 250 mm³ were scored as tumor positive. Shown are pooled data from 2 independent experiments with a total of 12–13 T cell reconstituted mice. Primary tumor growth was analyzed in untreated Rag^-/- and Rag^-/-IL-7R^-/- mice (n = 3). Statistical significance was calculated using the log-rank test. (C) The numbers of splenic DCs were determined in tumor-bearing mice 28–37 days after tumor challenge. Pooled data (±SEM) from 2 independent experiments with a total of 6–11 mice/group are shown. Statistical significance was calculated using the Mann-Whitney test.</p