“Low-Tech” Innovations

This paper is about an industrial sector which, according to the usual socio-scientific indicators, is referred to as “low-tech”, respectively as non-research intensive and which mostly comprises “traditional” industries. The interest in this sector is motivated by the contradictory situation that, on the one hand, the debate about the perspectives of modern societies focuses on the rapidly growing importance of technological innovations, knowledge and research-intensive economic sectors while, on the other hand, traditional industries make up a considerable fraction of employment and production, especially also in developed economies. On the basis of the results of extensive empirical research, this contribution tries to find answers to the basic question, whether one can speak of an innovation mode typical of the low-tech sector. The institutional based innovation systems approach forms the categorical basis of the analysis. In order to elucidate the specific features of low-tech innovations, they are, in conclusion, compared to the general characteristics of high-tech-based innovation processes.     

Guides “bimorphes” d''ondes ultrasoniques “bimorph” ultrasonic wave guides”

An analysis of the dispersion of elastic waves is presented for two types of long ultrasonics wave-guides that we qualify of “bimorph”: (i) a “three-layer” guide made of two different materials and (ii) a “clad core” guide built up of a rectangular core surrounded by a cladding, the materials of the rod and cladding having different properties. An analytical model is proposed to describe the extensional, flexural and torsional motions in “bimorph” wave guides having two geometrical and material symmetry axes. The asymptotic behaviour of the model allows one to select the material properties which lead to modes guided essentially either in the central layer or in the core of the bimorph guide. Moreover, the dispersive properties of a “bimorph” can be controlled through the choice of geometrical and material parameters.     

“Optimizing the Interaction Between the Food and Drug Administration and the Industry” The Need for Cooperation for the “Public Good”

It is a pleasure for me to be a speaker at this conference, to share the podium with a friend and former colleague, Merve Schumate, of the FDA and also to have the opportunity to appear for the first time with Dr. Parariello of Wyeth Laboratories. The title for this morning's session, “Optimizing the Interaction Between the Food and Drug Administration and the Industry”, is an interesting one. As I was preparing my remarks, I wondered if they would be different if I was giving this talk to an FDA seminar at the agency or at the Public Citizen Litigation Group, Nader's organization. If I was talking to Dr. Sidney Wolf of the Litigation Group, I m sure that his optimization plan between FDA and the Industry would be tied to the concept of having open files, everything in writing and memoranda for all meetings. I feel fairly certain that Dr. Wolf would wish to have the opportunity to have either himself or one of his colleagues attend any of the meetings that they thought worthy of their time and effort. Now if I was an FDA reviewer and was talking about optimizing the interaction, I would see Industry representatives submitting well researched NDA files and supplements. These Industry representives would quickly understand and appreciate the wisdom of my request for additional studies, more data for the NDA, and the use of certain terms and concepts in relationship to labeling and promotional activities. They would find my suggestion of a patient package insert to be extremely helpful. On the other hand, if I were to become one of Dr. Papariello's researchers, I'm sure that I would see optimization of the system occur when my explanation to the FDA reviewer was quickly understood, all my views on the relationship of the data to the study submitted were accepted without question, and the agency looked most favorably on everything that was submitted to support the application.     

Interfacing the Cell with “Biomimetic Membrane Proteins”

Integral membrane proteins mediate a myriad of cellular processes and are the target of many therapeutic drugs. Enhancement and extension of the functional scope of membrane proteins can be realized by membrane incorporation of engineered nanoparticles designed for specific diagnostic and therapeutic applications. In contrast to hydrophobic insertion of small amphiphilic molecules, delivery and membrane incorporation of particles on the nanometric scale poses a crucial barrier for technological development. In this perspective, the transformative potential of biomimetic membrane proteins (BMPs), current state of the art, and the barriers that need to be overcome in order to advance the field are discussed.     

“In Vitro” - “In Vivo” Correlations of Eight Nitrofurantion Tablet Formulations: Effect of Various Technological Factors

Abstract

The bioavailability of eight nitrofurantoin tablet formulations differing in technological respects has been evaluated and correlated with de dissolution curves obtained using USP XXI Ed methods I and II. Method I was found incapable of predicting bioavailability of formulations when Carbopol 934 is used as binder. The influence of the technological factors varied is discussed.     

“Style” and technology

A rational approach to dealing with the problems created by developing technologies requires a new account of what is involved in proper management. A tripartite distinction is introduced between being reasonable, being rational, and having style. These notions are based on the commonsense principle of rationality (CPR), to be rational one must learn from experience. The proper management of technology requires more than learning from experience (being rational) and having the proper goals (being reasonable); it requires style, which entails being reasonable and acting in accordance with a given standard systematically over time.     

The “Ductilities” in Single Phase Steels from Usual to Nanoscale Microstructures

The control and the improvement of the ductility of nanostructured structural steels is one of the key challenges in assessing the technological viability of this metallurgical strategy. In the present paper, it is shown that more rigorous definitions of the ductility are required in order to avoid possible confusions. After this preliminary work, a more transparent analysis is done concerning the effect of the microstructural scale showing clearly the weaknesses and the strengths of ultra‐fine single phase steels. Finally, possible ways to overcome the main limitations are presented.     

Differentiation between the terms ”confined masonry“ and ”infill masonry“

This publication concerns the differentiation between the terms ”confined masonry“ and ”infill masonry“ using the example of the national technical approval Z‐17.1‐1145 – POROTON S9 MW –vertically perforated clay units with integrated thermal insulation using thin layer mortar [1].     

In Vitro “Wound” Healing: Experimentally Based Phenomenological Modeling

We discuss the applicability of some elementary models for the closure of in vitro “wounds” that are inflicted in monolayer cell cultures (also termed “wound healing assays”). These models can be applied to the simulation of healing of superficial wounds as long as they only concern the epidermis. We test several models that are based on a curvature driven displacement, a simple partial differential equation based model in which the actual cellular density is tracked. Finally, a semi‐stochastic cellular based model is evaluated.     

Testing of “In Vitro” Dissolution Behaviour of Microparticulate Drug Delivery Systems

No official dissolution method exists concerning microparticulate drug delivery systems. The purpose of this work is the evaluation of different dissolution methods commonly used to test the in vitro release behaviour of microparticulate drug delivery systems. The influence of different environmental conditions, as stirring speed, ionic strength and presence of surfactant, on drug release is also evaluated.

Four dissolution methods, based on different equipments (USP dissolution test apparatus, rotating bottle apparatus, shaker incubator, recycling flow through cell), are performed on the same batch of indomethacin loaded poly-D, L-lactide (PDLLA) microspheres prepared by spray drying. The results obtained with the methods tested show the influence of in vitro dissolution method employed and of the environmental conditions on drug release profile.     

“In Vitro” Studies on Buccoadhesive Tablet Formulations of Hydrocortisone Hemisuccinate

Different bioadhesive and matrix-forming polymers were evaluated using “in-vitro” tests to identify a potentially convenient “in-vivo” formulation for the sustained delivery of hydrocortisone hemisuccinate to the oral cavity. The selected composition allows an erosion-diffusion mechanism coherent with the low hydrosolubility of the drug and with potential advantages for both the patient and the manufacturer.     

A Rebuttal to The “Reply”

At the outset a brief background from a pharmaceutics perspective is presented here. Pharmaceutical industry is one of the most tightly regulated industries. Statistics naturally plays an important role in the implementation of the compendial, regulatory and in-house requirements. The minimal requirement consists of a set of basic statistics, such as mean and standard deviation (SD), associated with each group of sample experimental data intended for submission. However, not only each statistic is individually subjected to a set of compendial, regulatory and in-house specifications, but also the individual observation is required to be within specific range for compliance (e.g. content uniformity). Hence these basic statistics are often referred to as the stand-alone sample (SAS) statistics, meaning that each statistic has to meet its own requirements. In this context, the geometric mean is indeed a SAS statistic. It is meaningful and interpretable directly from its face value. The geometric standard deviation (GSD) as derived in ref(B) is also a (SAS) statistic. It is meaningful and easily interpretable directly from its face value. It has the same sample information and the same interpretation as that of the regular SD. Sometimes, it shares essentially the same magnitude as the regular SD. Besides, it also has essentially the same magnitude as that of the jackknife GSD statistic, GSD(JK). For decades, these geometric statistics have been in practice, particulary, since the author of ref(B) was a member of the USP In-Vitro Bioavailability Testing Subcommittee (1970-1975). It has also been accepted fully and freely by the above-mentioned over-sight agencies.     

“Snowing” Graphene using Microwave Ovens

Developing a simple and industrially scalable method to produce graphene with high quality and low cost will determine graphene's future. The two conventional approaches, chemical vapor deposition and liquid‐phase exfoliation, require either costly substrates with limited production rate or complicated post treatment with limited quality, astricting their development. Herein, an extremely simple process is presented for synthesizing high quality graphene at low‐cost in the gas phase, similar to “snowing,” which is catalyst‐free, substrate‐free, and scalable. This is achieved by utilizing corona discharge of SiO₂/Si in an ordinary household microwave oven at ambient pressure. High quality graphene flakes can “snow” on any substrate, with thin‐flakes even down to the monolayer. In particular, a high yield of ≈6.28% or a rate of up to ≈0.11 g h^?1 can be achieved in a conventional microwave oven. It is demonstrated that the snowing process produces foam‐like, fluffy, 3D macroscopic architectures, which are further used in strain sensors for achieving high sensitivity (average gauge factor ≈ 171.06) and large workable strain range (0%–110%) simultaneously. It is foreseen that this facile and scalable strategy can be extended for “snowing” other functional 2D materials, benefiting their low‐cost production and wide applications.     

Preparation of Langmuir-Blodgett “built-up” multilayer films of a lightly substituted model aromatic, anthracene

It is generally considered almost impossible to make Langmuir-Blodgett “built-up” multilayer films of conjugated (aromatic) molecules unless their aromaticity is very heavily diluted with aliphatic substituents or molecules; this severely limits the scientific and technological applications of such films. For example, even to handle anthracene-derivative monolayers on water (without any attempt to transfer them to a substrate) has in the past required the anthracene to be substituted with an aliphatic side chain containing at least twelve carbon atoms; this prevents instability of the water-borne monolayer. As a result, the interesting and useful electrical and optical properties which conjugated multilayers would be expected to possess (because of the extended molecular π electron systems) are heavily diluted by aliphatic properties. We now report the successful deposition of high quality multilayers of lightly substituted anthracene derivatives, with aliphatic side chains as short as four CH₂ units. Improved techniques may well permit even shorter side chains to be used. We describe the deposition methods in detail and give experimental evidence that high quality films from one monolayer thick (about 1.5 nm) to 500 monolayers were indeed obtained; the interesting electrical and optical properties of these films, and their unique structure, will be discussed in detail at a later date. If these preparation techniques can be extended to other conjugated systems, as seems likely, the range of highly organized structures which can be constructed by the Langmuir-Blodgett method has been greatly increased, and the prospects for its technological use (in applications ranging from electronic devices to high temperature superconductors) have been improved.