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Nanoparticle-based delivery systems have shown great promise for theranostics and bioimaging on the laboratory scale due to favorable pharmacokinetics and biodistribution. In this study, we examine the utility of a cage-forming variant of the protein lumazine synthase, which was previously designed and evolved to encapsulate biomacromolecular cargo. Linking antibody-binding domains to the exterior of the cage enabled binding of targeting immunoglobulins and cell-specific uptake of encapsulated cargo. Protein nanocages displaying antibody-binding domains appear to be less immunogenic than their unmodified counterparts, but they also recruit serum antibodies that can mask the efficacy of the targeting antibody. Our study highlights the strengths and limitations of a common targeting strategy for practical nanoparticle-based delivery applications. ISSN:1554-8929 ISSN:1554-8937

Mono-glucosylation of (H/K/N)Ras by Clostridium sordellii lethal toxin (TcsL) blocks critical survival signaling pathways, resulting in apoptotic cell death. One yet unsolved problem in studies on TcsL is the lack of a method allowing the specific detection of (H/K/N)Ras glucosylation. In this study, we identify the Ras(Mab 27H5) antibody as a glucosylation-sensitive antibody capable for the immunoblot detection of (H/K/N)Ras glucosylation in TcsL-treated cells. Alternative Ras antibodies including the K-Ras(Mab F234) antibody or the v-H-Ras(Mab Y13-159) antibody recognize Ras proteins regardless of glucosylation. (H/K)Ras are further shown to be more efficaciously glucosylated by TcsL than Rac1 in rat basophilic leukemia cells as well as in a cell-free system.Structured summaryMINT-7261742: TcsL (uniprotkb:Q46342) enzymaticly reacts (MI:0414) H-RAS (uniprotkb:P01112) by enzymatic studies (MI:0415)MINT-7261729: TcsL (uniprotkb:Q46342) enzymaticly reacts (MI:0414) Rac1 (uniprotkb:P63000) by enzymatic studies (MI:0415)MINT-7261772: TcsL (uniprotkb:Q46342) enzymaticly reacts (MI:0414) K-RAS (uniprotkb:P01116) by enzymatic studies (MI:0415)MINT-7261784: TcsL (uniprotkb:Q46342) enzymaticly reacts (MI:0414) N-RAS (uniprotkb:P01111) by enzymatic studies (MI:0415)

The following essay is based on an unfinished manuscript left by my husband. The original manuscript consists of a treatise on the freedom of the will which contains several fragmentary inserts, and a separate fragment on the freedom of action. These papers were written in 1951 and antedate the manuscripts of the French lectures he gave at the Sorbonne in June 1952 under the title of ‘Les fondements logiques de la mecanique des quanta’ [1952d], and of his books Nomological Statements and Admissible Operations [1954e] and [1976a], and The Direction of time [1956b].

The term ‘philosophy of nature’ has recently acquired new significance. A new scientific philosophy, arising from the results of scientific research and dedicated to rigorous standards, is beginning to take shape. It has offered unexpected solutions to a number of old problems and has raised several novel questions whose existence had been overlooked at earlier times. The status of this new philosophy of nature is the topic of the following investigation.

University reform must begin with a critique of science [Wissenschaft, or organized knowledge]. Not a logical critique, such as is offered in epistemology, but an evaluation; that is to say, the ultimate meaning, the ultimate significance of science for humanity must be set forth. For one thing is clear: service to science remains the essential task of the university, and any move towards reform that does not keep such service squarely at the center of its field of vision is doomed to failure from the start.

Professor Hans Reichenbach. who teaches at the University of Berlin, is a proponent of the new scientific trend in philosophy. It is the aim of this new movement to construct a precise theory concerning our knowledge of nature and the relation between thought and existence by means of a thorough investigation of the natural sciences, including mathematics; for this reason, it is more closely bound up with the empirical sciences than any other philosophical movement. The teachings of this new philosophy of science are still a matter of controversy today, facing particularly strong opposition among humanistic and cultural philosophers. This may enhance the interest of our readers in the following interview, in which this leading proponent of the movement shares with us his basic ideas.

That a cultural movement requires fifteen years from the time of its origin to develop and clarify its philosophical foundations does not tell in any way against the value of that movement. On the contrary, that action resting upon certain definite values precedes a clear recognition of these values, that an ideal clearly and distinctly enters the consciousness only long after the person acting under the influence of the emotion to which it gives rise has begun to attempt to realize by means of his actions his vaguely divined rather than clearly acknowledged end, is a frequently observed phenomenon. It is not clear, rational knowledge that gives an act its moral value, but rather the motive for it, independent of the intellectual processes which accompany the action. Yet that does not mean that a clear formulation of one’s own volitional decision is unnecessary. On the contrary, a person undergoing progressive development will endeavour to determine clearly and explicitly the precise nature of the goal of all his laborious efforts, which so often are repaid only with ingratitude. He will make this endeavour because he wishes his action to be consistent, because he wants all his activities to conform to his one great ideal, because nothing but the clear recognition of his own ultimate end gives him the proper strength to fight for it.

This extensive work by Rudolf Carnap represents a massive compilation of his ideas on logic and epistemology. Yet it is not Carnap’s ideas alone but also those set forth by the Vienna Circle as a scientific conception of the world which have been fully presented for the first time in Carnap’s major work. “The basic orientation and the line of thought of this book are not property and achievement of the author alone but belong to a certain scientific atmosphere which is neither created nor maintained by any single individual. The thoughts which I have written down here are supported by a group of active or receptive collaborators. This group has in common especially a certain basic scientific orientation. That they have turned away from traditional philosophy is only a negative characteristic. The positive features are more important; it is not easy to describe them, but I shall try to give a loose characterization. The new type of philosophy has arisen in close contact with the work of the special sciences, especially mathematics and physics. Consequently they have taken the strict and responsible orientation of the scientific investigator as their guideline for philosophical work, while the attitude of the traditional philosopher is more like that of a poet. This new attitude not only changes the style of thinking but also the type of problem that is posed. The individual no longer undertakes to erect in one bold stroke an entire system of philosophy. Rather, each works at his special place within the one unified science. For the physicist and the historian this orientation is commonplace, but in philosophy we witness the spectacle (which must be depressing to a person of scientific orientation) that one after another and side by side a multiplicity of incompatible philosophical systems is erected. If we allot to the individual in philosophical work as in the special sciences only a partial task, then we can look with more confidence into the future: in slow careful construction insight after insight will be won. Each collaborator contributes only what he can endorse and justify before the whole body of his co-workers. Thus stone will be carefully added to stone and a safe building will be erected at which each following generation can continue to work.”

It is a noteworthy fact that the Catholic Church exercises a persistent influence not only upon the general population but also upon the leadership of academic circles. The Church maintains this influence with the help of the powerful edifice of her philosophy, which she calls the only true philosophy, and she expresses this influence through the large number of Catholic student fraternities, as well as through the more loosely organized groups of Catholic students, such as the Free Association of Free Catholic Students and the various Catholic student organizations that perform charitable work. All the young students who are banded together in these groups appeal, in scientific disputes, to the Catholic philosophy. It is the scientific shield with which the educated Catholic, who acknowledges the validity of scientific thinking in other spheres, protects himself whenever he is attacked on religious grounds.

The Socialist Students’ Party has given me the task of outlining in this initial essay their university program. This essay is the first in a series of pamphlets presenting to the public the demands and the plans of the Socialist Students.

Since the time of their first publication, Godel’s results have been considered as a serious blow against Hilbert’s program of proving the consistency of mathematics. If the consistency of a system cannot be proved within the system itself but only in the metalanguage, a proof of consistency seems valueless because we do not know whether the language within which the proof is given is consistent. It was Hilbert’s program to secure the reliability of ordinary mathematical proofs by giving a proof of the consistency of the mathematical language. If it turns out with Godel’s second theorem that this proof can only be given in another language whose consistency is not proved, this seems to show that Hilbert’s program cannot be carried through because it leads into an infinite regress.

Albert Einstein has been awarded the Nobel Prize. After the enormous popularity that the creation of the theory of relativity has brought to this great man, this distinction will hardly come as a surprise to the general public. What is surprising is that the citation from the Swedish Academy of the Sciences does not mention the theory of relativity, but specifically honors Einstein for a different achievement: “for his investigations in the field of theoretical physics, and especially for his discovery- of the law of the photoelectric effect”. It would seem that the Swedish Academy wished to avoid taking a position on the question of the theory of relativity — in itself a display of justifiable caution, since the Nobel Prize ought not to render a decision in scientific disputes. Nonetheless, the Nobel Committee has thereby rejected the historic opportunity to do public honor to one of the greatest physical theories of all time.

That it is possible today to speak of philosophical research can itself be regarded as a characteristic of modern philosophy. For the very word ‘research’ designates a method. In admitting that it engages in research, philosophy classifies itself, from the methodological standpoint, among the special sciences, which progress step by step by solving particular problems and attain a systematization of the whole only by assembling the various components of knowledge embodied in these situations.

To speak of ‘the student’ is, from the outset, an undertaking doomed to failure, for the student body is not at all uniform. Rather, it is great multitude composed of a variety of individuals, each one of whom possesses an entirely separate character and his own special leanings; a single type of student is not to be extricated from the mass. Yet it is a singularly agitated mass, full of deep stirrings and aspirations; it is, if I may so put it, vital through and through. Movements arise which aim to fire the student with enthusiasm for art, literature, and a broad cultural education; others wish to train him to be a citizen with a concern for politics; others, again, present to him an untroubled life of pleasure as the highest ideal; and still others wish to steel his character by means of systematic physical training. It is a play of waves, in constant motion, and there are as many waves as there are students. Yet there are greater waves and lesser waves, and some combine to from larger complexes. Parties are formed among the student body. Among others, we find the fraternal organizations [eine korpsstudentische und eine burschenschaftliche Partei]; German nationalist, liberal, and socialist parties; Catholic, Protestant, Jewish, and free-thinking parties; organizations dedicated to strengthening the body and the will by means of physical exercises and abstinence from alcohol; parties aiming at the social activation of students; and parties promoting a more thorough professional education or a better liberal general education.

To make use of a philosophical concept in practical thinking is one thing, to render a pure and meaningful formulation of the concept quite another. Everyone faces the necessity of judging the truth of various assertions, and in daily life, as in science, methods have been developed in accordance with which we more or less consciously make such judgments. But the meaning of truth is not given along with the use of the concepts; it can only be grasped by philosophical reflection upon the sense and meaning of the processes of knowledge. To give you a glimpse into such epistemological research is my purpose today.

The philosophical content of modem science has found perhaps its clearest expression in the widespread interest of the public in Einstein’s theory of relativity. While this interest set in, of course, only after the theory had taken firm root in physical circles, and while it is certainly riddled with misunderstandings of the physical theory, it is nonetheless only to be explained by the fact that the theory resolves more than merely technical problems, that it touches upon genuinely philosophical issues the intellectual consequences of which are of a significance similar to that of Copernicus’ discovery in his day.

A description of the contemporary state of the exact sciences has not always presented as difficult a task as it does in our time. Over the course of the development of a science there are periods of ascent and periods of lingering at a plateau. Both are essential for the progress of science, for although the ascent constitutes the period of actual growth, the time of quiet elaboration, of the gradual maturation of newly made discoveries, is equally necessary for the internal consolidation of the whole developmental process. The distinctive rhythm of all life, the step-by-step progress, in which ascent and a time for maturing alternate with one another, appears to be intrinsically necessary for the over-all development of sociological phenomena, to which the growth of the natural sciences bears a living testimony. After the steep ascent accomplished in the era of such scientists as Galileo and Newton, the succeeding century coincided with a period of undisturbed consolidation, but about one hundred years ago a new ascent was begun which even today has not yet flattened out into a horizontal curve. On the contrary, over approximately the last three decades we may observe a substantially steeper ascent of the curve than was to be seen before, for our epoch is characterized by overly hasty development, by the appearance of totally new and revolutionary theories of fundamental significance, by the amassing of new discoveries, so that the contemporary observer barely recalls the impression of steady progress and finds the image of growth by fits and starts to accord far better with his experience.

On November 15, three hundred years will have passed since Johannes Kepler, one of the founders of modern astronomy and of modem science as a whole, closed his eyes for the last time. Measured against the brevity of our own individual lives, three hundred years is a long time, but measured with an eye to the laborious progress of science as a social phenomenon of civilization, it is but a short span of time, encompassing such a closely related set of intellectual approaches that, from this stand-point, Johannes Kepler is regarded as a member of the present epoch of civilization — indeed, as one of those leading minds whose thoughts continue to be applied in new ways by scientists.

The Socialist Student Party was formed by a group of socialist students of all political directions who had come together in secret prior to the revolution, and some of whom had participated in the revolution. The Party made its first public appearance at a general student meeting one week after November 9th: its united stand and, even more, its very existence caused the greatest amazement, which soon was to change into open hostility. Our appearance caused students in Berlin who previously had been apolitical to organize themselves into parties as well, and thereby the election of the then non-existent Student Council became possible. Nine representatives were elected on the basis of general, equal, secret and proportional representation. The election returns (230 votes in our favor) permitted us to send at least one of our representatives to the Student Council.

There are those who have called our era unphilosophical and held its achievements to be confined to technology and science. To the more discerning eye, however, this judgment appears unjustified, for it employs the wrong standard. To be sure, we do not find in our day philosophy as it was understood in past centuries, philosophical systems and world views — or where we do find these, they are mere pale reflections of past systems. Instead, the real philosophy of our day has developed along with the positive sciences and can only be discovered if we keep our eyes open for the special form of philosophical thinking that is an outgrowth of the construction of scientific concepts and the mental apparatus of the sciences. This philosophy has, to be sure, not yet become an objective system; for the present it is more a cast of mind than a store of factual results, and its development into a science along the lines of the other sciences is reserved for the future. This is the reason that there is so little awareness of this new philosophy. There are probably a good many philosophically minded professional scientists, but there are few philosophers. The following remarks are dedicated to one of these, the worthiest representative of such a philosophy of the positive sciences: Bertrand Russell.

If we were to list the elements that characterize the life of the general population in our time, we would undoubtedly have to place at the top of the list a strong interest in the cultivation of the body, an effort to improve physical health. There is no question but that the numerous athletic movements, such as hiking, gymnastics, fencing, swimming, ball games, skiing, boating, have won over a large portion of the population. The power of the old fogey who previously enjoyed great respect because of the great circumference of his beer belly and his immense physical sloth has gone into a decline and is receding daily. Slender, sinuous bodies that have willingly developed a capacity for strenuous tasks are becoming increasingly the ideal of our people. As a result, numerous societies and unions have sprung up with the intent of bringing about physical development, especially in the young, in a great variety of ways.

It is the lot of philosophy not to enjoy, as do other sciences, a more or less independent existence, but to grow and flourish in tandem with the development of the special sciences. Never has there existed philosophical investigation ‘as such’, resolving philosophical problems through its own springs of knowledge during periods of stagnation in the sciences. Rather, philosophical problems are not seen with all their ramifications, philosophical puzzles not really thoroughly thought out, until investigations in the individual sciences have encompassed a broad range of knowledge and the process of learning has reached a certain maturity, which forms the only possible basis for philosophical activity. We need only recall the philosophy of Plato, which evolved out of a serious concern for mathematics, or the grand system of Kant, which, while purporting to be a system of pure reason, actually represents a thoroughgoing reworking of the mathematical physics of the eighteenth century, which accounts for its overwhelming importance.

The city of Prague houses two artifacts that serve as a landmark in the history of civilization: two sextants of the famous Danish astronomer, Tycho Brahe. Tycho, who lived in the latter half of the sixteenth century and who was widely famed throughout the world as an astronomer, made his home on the Danish island Hveen, where King Frederick the Second of Denmark had a castle, the Uranienborg, built for him. Here, by using various newly constructed mechanical devices, he prepared his instruments, which superseded all their predecessors in their eminent precision and with which he himself undertook very exact observations of the planets. But under Frederick’s successor, Christian. Tycho’s luck turned. Some jealous courtiers were able to turn the king against him, and after 21 years of successful activity, the 51-year-old Tycho had to flee from Uranienborg. He came to Germany, a country with which he had become familiar as a student, and spent two years in Wandsbek as a guest of Count Rantzau. From thence he was called to Prague, having received an appointment from Emperor Rudolph the Second, and he succeeded in having his instruments from Uranienborg sent after him. In Prague he continued his observations with the support of the young Kepler, but he died of a sudden illness after only two years. Kepler took over his instruments and continued his observations. Fate was unkind to these valuable treasures, for almost all of them were destroyed during the Battle of White Mountain.

With the death of Svante Arrhenius, the world has lost a scholar whose personality and work became the embodiment of a new era in the exact sciences: the era of the fusion of two basic sciences, physics and chemistry. If the great development that took place in both sciences in the first three-quarters of the nineteenth century can be credited to their separation and the concentration of efforts within a narrower sphere that it made possible, then the blossoming experienced by both sciences in the last quarter of the century is to be attributed equally to the fact of their coming together. This unification was given visible expression in the concept of physical chemistry, the name given to the common border area. If we were to assign to Arrhenius a professional classification. we would have to call him a physical chemist.

The Socialist Students’ Party is a coalition of students and faculty members who believe in socialism.

From October 23 to October 27, the scientific world will be celebrating the one-hundredth birthday of Marcellin Berthelot. This great French chemist has not yet achieved the status of a remote historical personality. It was a mere twenty years ago that he died, and some of the leading scholars of today had occasion to engage with him in scientific dispute. Nonetheless, his lifetime is sufficiently removed from the present for us to survey his works and his influence and to construct a clear picture of his significance.

The overriding idea for bringing out the present volume in the Vienna Circle Collection was the intention of publishing a selection of those popular and scientific articles by Hans Reichenbach that so far have not been available in an English translation or that at this time are out of print in English.

Last year a conference on the epistemology of the exact sciences was held in Prague in connection with the conference of mathematicians and physicists. This year, the congress of physicists, mathematicians, and natural scientists held in September in Konigsberg was made the occasion for a second conference on this subject.