Muscle-specific, liver-detargeted adeno-associated virus gene therapy rescues Pompe phenotype in adult and neonate Gaa-/- mice.

Pompe disease (PD) is a neuromuscular disorder caused by acid α-glucosidase (GAA) deficiency. Reduced GAA activity leads to pathological glycogen accumulation in cardiac and skeletal muscles responsible for severe heart impairment, respiratory defects, and muscle weakness. Enzyme replacement therapy with recombinant human GAA (rhGAA) is the standard-of-care treatment for PD, however, its efficacy is limited due to poor uptake in muscle and the development of an immune response. Multiple clinical trials are ongoing in PD with adeno-associated virus (AAV) vectors based on liver- and muscle-targeting. Current gene therapy approaches are limited by liver proliferation, poor muscle targeting, and the potential immune response to the hGAA transgene. To generate a treatment tailored to infantile-onset PD, we took advantage of a novel AAV capsid able to increase skeletal muscle targeting compared to AAV9 while reducing liver overload. When combined with a liver-muscle tandem promoter (LiMP), and despite the extensive liver-detargeting, this vector had a limited immune response to the hGAA transgene. This combination of capsid and promoter with improved muscle expression and specificity allowed for glycogen clearance in cardiac and skeletal muscles of Gaa-/- adult mice. In neonate Gaa-/- , complete rescue of glycogen content and muscle strength was observed 6 months after AAV vector injection. Our work highlights the importance of residual liver expression to control the immune response toward a potentially immunogenic transgene expressed in muscle. In conclusion, the demonstration of the efficacy of a muscle-specific AAV capsid-promoter combination for the full rescue of PD manifestation in both neonate and adult Gaa-/- provides a potential therapeutic avenue for the infantile-onset form of this devastating disease.

Efficient Unitary Designs with a System-Size Independent Number of Non-Clifford Gates.

Many quantum information protocols require the implementation of random unitaries. Because it takes exponential resources to produce Haar-random unitaries drawn from the full n-qubit group, one often resorts to t-designs. Unitary t-designs mimic the Haar-measure up to t-th moments. It is known that Clifford operations can implement at most 3-designs. In this work, we quantify the non-Clifford resources required to break this barrier. We find that it suffices to inject O ( t 4 log 2 ( t ) log ( 1 / ε ) ) many non-Clifford gates into a polynomial-depth random Clifford circuit to obtain an ε -approximate t-design. Strikingly, the number of non-Clifford gates required is independent of the system size - asymptotically, the density of non-Clifford gates is allowed to tend to zero. We also derive novel bounds on the convergence time of random Clifford circuits to the t-th moment of the uniform distribution on the Clifford group. Our proofs exploit a recently developed variant of Schur-Weyl duality for the Clifford group, as well as bounds on restricted spectral gaps of averaging operators.

Morphological study of the anatomical variations of anterior belly of digastric muscle in Brazilian cadavers.

BACKGROUND: Cases of variations in anterior belly of the digastric muscle must be carefully identified to avoid misinterpretations and assist in the correct surgical or aesthetic procedure and help in the teaching of anatomy. The aim of this study was to describe the anatomical variations of anterior belly of digastric muscle in Brazilian cadavers. MATERIALS AND METHODS: Thirty-one human heads were selected, from adult cadavers (18-80 years, 29 males and 2 females). The morphology of the anterior belly of the digastric muscle was observed, identifying the possible anatomical variations that were characterised and classified according to the amount of muscle bellies, fibre direction and place of origin and insertion. The morphometric measurements were performed using a digital calliper. To analyse the data obtained, photographic documentation, anatomical description and individual morphometric description of each muscle belly were performed. The incidence of anatomical variation was obtained in percentage (%). RESULTS: The anatomical variation of the anterior belly of the digastric muscle was present in 6 cadavers (19.31%; 1 female and 5 male). All anatomical variations presented an accessory belly to the anterior belly. However, these accessory bellies were configured differently in the location, direction of muscle fibres and in their dimensions (length and width). CONCLUSIONS: The gross anatomy of the anterior belly of the digastric muscle and their variations is important to assist in surgical procedures, pathological or diagnostic function. In addition, asymmetrical variations in the submental region must be carefully identified to avoid misinterpretations.

Chore or desire? Students' response to online lessons in scientific integrity.

One of the main responsibilities of universities for their students, researchers, and society is to teach scientific integrity. Over the years, many universities-including RWTH Aachen University-have developed modules to impart the rules of good scientific practice. The current case study outlines the "Scientific Integrity" online course of RWTH Aachen University that has been offered to all master's students starting in October 2020; it explains to what extent the topic of scientific integrity meets genuine interest among students. Based on the online questionnaires that students were asked to fill out before starting the course (Q1) and after completing the course (Q2), it was verified that the implemented course achieved a satisfactory, but expandable acceptance. 57% of study participants initially (Q1) strongly affirmed to be interested in the topic; said percentage increased to 65.3% at the end of the course (Q2). While at the time of Q1 most students admitted that they would not take the course if it were voluntary, the majority of study participants came to the opposite conclusion after the course (Q2). The results suggest that the assessment of the relevance of the course may be dependent on familiarity with its contents.

Forced to join the Waffen-SS? Chief pharmacist Victor Capesius (1907-1985) and his role in Auschwitz concentration camp.

Victor Capesius (1907-1985) attained sad fame as chief pharmacist in the Auschwitz concentration camp. After the war he outlined himself as a victim of his time and claimed to have been forced into the Waffen-SS as a so-called Romanian "Volksdeutscher" (ethnic German). But does this claim stand up to critical scrutiny? What was his actual role in Auschwitz, how did his life develop in the postwar period, how did he himself evaluate his actions in the Third Reich, and to what extent do self-image and historical facts coincide? These are precisely the questions that this article explores. The study is based on primary sources from various archives. These are supplemented and compared with the existing literature on Capesius, the role of pharmacists in the Third Reich, and the Auschwitz concentration camp.
The analysis shows that Capesius was not only complicit in the criminal acts in the concentration camp, but directly involved in the systematic killing of thousands of Jewish people - among other things, by dispensing Zyklon B and phenol and by the lethal selection of people at the ramp. The alleged compulsion to join the Waffen-SS, on the other hand, cannot be substantiated. After 1945, Capesius was imprisoned twice by the Allies, but only charged in the first Auschwitz trial in the 1960s. Despite a guilty verdict, he was released from prison as early as 1968. At the end of his life, Capesius could look back on a successful career as a pharmacist and businessman in Germany. At no time did he come to a self-critical evaluation of his role in the Third Reich.

In Vivo Pulp Temperature Changes During Class V Cavity Preparation and Resin Composite Restoration in Premolars.

OBJECTIVE: This in vivo study evaluated the influence of the sequence of all restorative steps during Class V preparation and restoration in human premolars on pulp temperature (PT). METHODS AND MATERIALS: Intact premolars with orthodontic extraction indication of 13 volunteers received infiltrative anesthesia and isolation with rubber dam. An occlusal preparation was made with a high-speed diamond bur under air-water spray until the pulp was minimally exposed, then a thermocouple probe was inserted within the pulp. A deep, 2.0-mm depth Class V preparation was made using a high-speed diamond bur under air-water spray. Three restorative techniques were performed (n=7): Filtek Z250 placed in two increments (10-second exposure, shade:A2, 3M ESPE, St. Paul, MN, USA), Filtek Z350 XT (40-second exposure, shade:A3D, 3M ESPE) and Tetric N Ceram Bulk Fill (10-second exposure, shade:IVA, Ivoclar Vivadent, Schaan, Liechtenstein), both placed in a single layer. Bonding layer and resin composite were exposed to light from the same Polywave LCU (Bluephase 20i, Ivoclar Vivadent). The peak PT and the difference between peak PT and baseline (ΔT) values were subjected to two-way, repeated measures analysis of variance (ANOVA), followed by the Bonferroni post-hoc test (α=0.05). RESULTS: Cavity preparation and etch & rinse procedures decreased the PT values (p<0.001). The 40-second exposure of Filtek Z350 caused the highest peak PT values (38.7±0.8°C) and the highest ΔT values (3.4±0.8°C), while Tetric N Ceram Bulk Fill showed the lowest values (-1.6±1.3°C; p=0.009). CONCLUSION: None of the evaluated procedures resulted in a PT rise near to values that could offer any risk of thermal damage to the pulp.

Functional Capacity Evaluation Research: Report from the Fourth International Functional Capacity Evaluation Research Meeting.

Purpose To summarize progress of functional capacity evaluation (FCE) research based on the proceedings of the Fourth International FCE Research Conference held in Switzerland on September 21 and 22, 2018. Methods A scientific committee identified key issues in FCE research and developed the program including key note presentations, a call for abstracts, and round table discussions over 2 days. Highlights of the presentations and discussions are summarized in this article. Results Seventy-nine participants from 11 countries attended the conference where 10 keynote lectures and 21 abstracts were presented. There was also an open discussion regarding the need for an International FCE clinical practice guideline (CPG), methods for developing such a guideline, and practical next steps. Full program details and abstracts from this Fourth International FCE Research Conference are available from https://www.sar-reha.ch/interessengemeinschaften/ig-ergonomie.html . Conclusions Researchers and clinicians continue to increase the body of knowledge in the FCE field. A major finding of this conference is the diversity across the different FCE protocols and research groups as well as of the different uses of FCE across cultural and social economic systems. Next steps will include exploring the development of an international, interdisciplinary, evidence-based FCE clinical practice guideline by a committee formed at the conference.

The pathologist Philipp Schwartz (1894-1977) : From Nazi victim to initiator of the "Emergency Society of German Scholars Abroad".

Without a doubt, Frankfurt Pathologist Philipp Schwartz is one of the most iconic scholars in recent medical history. As the son of Jewish parents, he was forced to emigrate after Hitler seized power in 1933. Despite this repressive experience, he succeeded in founding the "Notgemeinschaft deutscher Wissenschaftler im Ausland" ("Emergency Association of German Scientists Abroad") in 1933, with which he helped hundreds of forcibly emigrated university teachers find academic positions. In addition, he had a decisive influence on the reform of the higher education system in Turkey, rendered outstanding achievements in neuropathology, and attained leading positions as a scientist in the exile countries Turkey and the USA.However, as successful as the pathologist's scientific career in exile may have been, his relationship with Germany remained problematic throughout his life. Against this background, this article focuses on the reception of Philipp Schwartz in the different political systems of Germany - from the Weimar Republic to the Third Reich, and from post-war Germany to the recent past in the Federal Republic. This study is essentially based on primary sources from the University Archive of Frankfurt.Schwartz had a promising career in the Weimar Republic. In the aftermath of Hitler's takeover (1933) he was deprived of any perspectives in Germany and fled to Switzerland in the spring of 1933. His achievements as a full professor in Istanbul and as initiator of the Notgemeinschaft are remarkable in both scientific and political regards. Still, he was denied employment at the Goethe University Frankfurt. Until well after his death (1977), Philipp Schwartz's life and work received little attention in Germany. It was only after the turn of the millennium that he received the recognition he was denied during his lifetime.

A career start in the Third Reich : The pathologist and Rudolf Virchow Award recipient Walter Müller (1907-1983).

The pathologist Walter Müller is undoubtedly one of the most prominent post-war representatives of his profession. He became full professor and founding dean in Essen, and in 1983 the German Society for Pathology (DGP) awarded him the Rudolf Virchow Medal - the highest distinction of the society - for his merits to the field of pathology.But this glorious career was by no means predetermined. Rather, after the end of the Second World War there were signs of a career break that were still largely unknown. After fleeing Königsberg from the approaching Red Army, Müller had to fear for his professional existence and his scientific advancement, as he was threatened with a ban on his profession in connection with denazification. As a young assistant doctor, Müller had joined the Berlin SA soon after the National Socialists took power and had also applied for membership of the NSDAP in 1937.Using Müller as an example, this article deals with the political influences and effects of National Socialism on young scientists and their career development. It poses the question of typical political barriers and overarching patterns of adaptation.On the basis of the personal written estate, personal archive sources, and a reanalysis of the available secondary literature, existing self-portrayals and narratives of Walter Müller are critically reviewed and supplemented. Several examples show that Müller's career development was characterized by a willingness to adapt politically. After a brief career slump in the years 1946/47, he succeeded in consolidating his career thanks to a mild denazification process and subsequently became one of the leading experts in German-language pathology.

The hepatopathologist Hans Popper (1903-1988) : An early victim of National Socialism in Austria.

In 1988, the "father of modern hepatology" Hans Popper died. His medical merits are numerous and outstanding and have already been praised many times. In particular, his research on liver diseases has gained widespread recognition. Much less well known is the fact that Popper was dismissed from the University of Vienna due to his Jewish ancestry after the "Anschluss" ("annexation") of Austria to the Third Reich and subsequently emigrated to the USA.Popper's biographers, who primarily belonged to his close circle of friends and colleagues, were unquestionably aware of this central caesura in Popper's life. However, the scientific analysis and presentation of this very event has been incomplete and, moreover, feeds heavily from the personal memories of the authors, which are inevitably subjective. For precisely this reason, the present contribution focuses on Popper's role as a politically persecuted Jew and the resulting implications.The study comes to the conclusion that Popper shows all the characteristics of a Nazi victim, namely a Jewish background, the dismissal from university, the threat of persecution by the Gestapo, and the subsequent forced emigration. Popper decided against remigration after 1945 and instead earned professional recognition in the USA and later worldwide. In the 1980s, Popper was criticized for his permissive attitude towards his former academic teacher, the doctor and Nazi criminal Hans Eppinger. Even if he did not completely succeed in making his behavior in the "Eppinger Case" understandable and comprehensible, the events gradually fell into oblivion, as evidenced by several recent posthumous statements of honor in German-speaking countries.

[The pathologist and "short-term rector" Albert Dietrich (1873-1961) and his ambivalent relationship with the Nazi regime : Not Nazi enough? German version]. / Der Pathologe und "Kurzzeitrektor" Albert Dietrich (1873­1961) und sein ambivalentes Verhältnis zum NS­Regime : Nicht nationalsozialistisch genug?

Throughout his professional life, the pathologist Albert Dietrich devoted himself to researching and combating cancer. Due to his considerable reputation and success, he was one of the first doctors to be awarded the Paracelsus Medal for his scientific services in 1952.However, Dietrich's role in the Third Reich was - and still is - far less defined. In May 1933, he became rector of the Eberhard Karls University in Tübingen, which at that time was one of the most Nazi-oriented universities. However, his term of office was short - by the end of 1933 he had already been replaced by the protestant theologian Karl Fezer.This article sheds light on Dietrich's ambivalent relationship to National Socialism and analyzes and discusses the background to his dismissal, his later (also politically influenced) emeritus status (1938/39), and his entry into the NSDAP, which took place at retirement age (1941). The study is based on archival sources partly evaluated for the first time and on a reanalysis of the relevant research literature.The study shows that Dietrich was targeted by individual Nazi decision-makers primarily because he advocated a supposedly "liberalist" university policy. Dietrich thus ultimately stands for a type of university lecturer who renounced a decidedly Nazi stance in public without, however, placing himself in a critical relationship to Nazi ideology. Against this background, statements from the postwar period that saw him retrospectively near Nazi opposition are to be classified as the formation of legends.

Obesity and surgical complications of pancreaticoduodenectomy: An observation study utilizing ACS NSQIP.

BACKGROUND: An estimated 38% of US adults are obese. Obesity is associated with socioeconomic disparities and increased rates of comorbidities, and is a known risk factor for development of pancreatic cancer. As a fourth leading cause of death in the United States, pancreatic cancer is commonly treated with a pancreatico-duodenectomy (PD), or Whipple procedure. Data regarding the effects of obesity on post-operative complication rate primarily comes from specialized centers, however the results are mixed. Our aim is to elucidate the effects that obesity has on outcomes after PD for pancreatic head cancer using a national prospectively maintained clinical database. METHOD: The 2010-2015 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) Participant Use Files (PUF) were used as the data source. We identified cases in which PD was performed (CPT code 48150) in the setting of a postoperative diagnosis of pancreatic cancer (ICD9 code 157.0). We excluded cases that had emergency admissions, BMI ≤18.5 kg/m2, intraoperative wound classification of III or IV, and disseminated cancer. Cases with missing BMI, preoperative albumin, operative time, LOS data were also excluded. Multiple imputation for missing sex, race, functional status, and ASA classification using chained equations was performed.16 Patients that had BMI ≥30 kg/m2 were considered obese, and patients with BMI <30 kg/m2 were used as control. RESULTS: 3484 patients underwent pancreaticoduodenectomy for pancreatic cancer. 860 patients were identified as obese. Propensity score analysis was performed matching age, sex, race, functional status, presence of dyspnea, diabetes, hypertension, acute renal failure, dialysis dependence, ascites, steroid use, bleeding disorders, history of chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), weight loss, American Society of Anesthesiologists (ASA) classification, and preoperative albumin levels. After matching, obese patients had higher risk of 30-day postoperative complications compared to control, including organ space wound infections (OR 1.38, 95% CI 1.07-1.79, p = 0.0128), returning to the operating room (OR 1.39, 95% CI 1.01-1.91, p = 0.0461), failure to extubate for greater than 48 h (OR 1.60, 95% CI 1.09-2.34, p = 0.0153), death (OR 1.68, 95% CI 1.01-2.78, p = 0.0453), septic shock (OR 2.22, 95% CI 1.46-3.38, p = 0.0002), pulmonary embolism (OR 2.42, 95% CI 1.07-5.45, p = 0.0332), renal insufficiency (OR 2.67, 95% CI 1.33-5.38, p = 0.0058). Sensitivity analysis yielded similar results with the exception of risk for return to the operating room, death, and pulmonary embolism, P > .05. CONCLUSION: In this large observational study using a national clinical database, obese patients undergoing PD for head of pancreas cancer had increased risk of postoperative complications and mortality in comparison to controls.

[Pathologists as victims of National Socialism : Results of a quantitative cross-sectional study]. / Pathologen als Opfer des Nationalsozialismus : Ergebnisse einer quantitativen Querschnittstudie.

AIMS OF THE STUDY: This explorative study focuses on those pathologists who became victims of the Third Reich by being dismissed, disenfranchised, persecuted, expelled, murdered, or driven to suicide. Accordingly, it examines the question of how many - and which - pathologists were oppressed in the Nazi dictatorship. It also looks at the reasons for this and the effects that repression has had on the lives of those affected - both in the Third Reich and in postwar Germany. MATERIAL AND METHODS: The study is based on archival source material, which was supplemented by a systematic evaluation of the relevant research literature. RESULTS AND DISCUSSION: In total, the biographies of 89 pathologists could be reconstructed and evaluated. Of these, 67 persons were persecuted for "racial" or anti-Semitic reasons. Until their disenfranchisement, the majority were employed at a university. The majority of the examined pathologists fled abroad, with most immigrating to the USA and Great Britain and successfully establishing themselves there professionally. No indications of a return to their homeland could be found in the sample presented here. Reasons included a lack of career options and negative personal experiences in postwar Germany, such as in reparation proceedings. Quite a lot of those who remained in the German Reich died violently, either in concentration camps or by suicide.

[A career start in the Third Reich : The pathologist and Rudolf Virchow Award recipient Walter Müller (1907-1983)]. / Ein Karrierestart im "Dritten Reich" : Der Pathologe und Rudolf-Virchow-Preisträger Walter Müller (1907­1983).

The pathologist Walter Müller is undoubtedly one of the most prominent post-war representatives of his profession. He became full professor and founding dean in Essen, and in 1983 the German Society for Pathology (DGP) awarded him the Rudolf Virchow Medal - the highest distinction of the society - for his merits to the field of pathology.But this glorious career was by no means predetermined. Rather, after the end of the Second World War there were signs of a career break that were still largely unknown. After fleeing Königsberg from the approaching Red Army, Müller had to fear for his professional existence and his scientific advancement, as he was threatened with a ban on his profession in connection with denazification. As a young assistant doctor, Müller had joined the Berlin SA soon after the National Socialists took power and had also applied for membership of the NSDAP in 1937.Using Müller as an example, this article deals with the political influences and effects of National Socialism on young scientists and their career development. It poses the question of typical political barriers and overarching patterns of adaptation.On the basis of the personal written estate, personal archive sources, and a reanalysis of the available secondary literature, existing self-portrayals and narratives of Walter Müller are critically reviewed and supplemented. Several examples show that Müller's career development was characterized by a willingness to adapt politically. After a brief career slump in the years 1946/47, he succeeded in consolidating his career thanks to a mild denazification process and subsequently became one of the leading experts in German-language pathology.

[The hepatopathologist Hans Popper (1903-1988) : An early victim of National Socialism in Austria. German version]. / Der Hepatopathologe Hans Popper (1903­1988) : Ein frühes Opfer des Nationalsozialismus in Österreich.

In 1988, the "father of modern hepatology" Hans Popper died. His medical merits are numerous and outstanding and have already been praised many times. In particular, his research on liver diseases has gained widespread recognition. Much less well known is the fact that Popper was dismissed from the University of Vienna due to his Jewish ancestry after the "Anschluss" ("annexation") of Austria to the Third Reich and subsequently emigrated to the USA.Popper's biographers, who primarily belonged to his close circle of friends and colleagues, were unquestionably aware of this central caesura in Popper's life. However, the scientific analysis and presentation of this very event has been incomplete and, moreover, feeds heavily from the personal memories of the authors, which are inevitably subjective. For precisely this reason, the present contribution focuses on Popper's role as a politically persecuted Jew and the resulting implications.The study comes to the conclusion that Popper shows all the characteristics of a Nazi victim, namely a Jewish background, the dismissal from university, the threat of persecution by the Gestapo, and the subsequent forced emigration. Popper decided against remigration after 1945 and instead earned professional recognition in the USA and later worldwide. In the 1980s, Popper was criticized for his permissive attitude towards his former academic teacher, the doctor and Nazi criminal Hans Eppinger. Even if he did not completely succeed in making his behavior in the "Eppinger Case" understandable and comprehensible, the events gradually fell into oblivion, as evidenced by several recent posthumous statements of honor in German-speaking countries.

[The pathologist Philipp Schwartz (1894-1977) : From Nazi victim to initiator of the "Emergency Society of German Scholars Abroad". German version]. / Der Pathologe Philipp Schwartz (1894­1977) : Vom NS-Opfer zum Initiator der "Notgemeinschaft deutscher Wissenschaftler im Ausland".

Without a doubt, Frankfurt Pathologist Philipp Schwartz is one of the most iconic scholars in recent medical history. As the son of Jewish parents, he was forced to emigrate after Hitler seized power in 1933. Despite this repressive experience, he succeeded in founding the "Notgemeinschaft deutscher Wissenschaftler im Ausland" ("Emergency Association of German Scientists Abroad") in 1933, with which he helped hundreds of forcibly emigrated university teachers find academic positions. In addition, he had a decisive influence on the reform of the higher education system in Turkey, rendered outstanding achievements in neuropathology, and attained leading positions as a scientist in the exile countries Turkey and the USA.However, as successful as the pathologist's scientific career in exile may have been, his relationship with Germany remained problematic throughout his life. Against this background, this article focuses on the reception of Philipp Schwartz in the different political systems of Germany - from the Weimar Republic to the Third Reich, and from post-war Germany to the recent past in the Federal Republic. This study is essentially based on primary sources from the University Archive of Frankfurt.Schwartz had a promising career in the Weimar Republic. In the aftermath of Hitler's takeover (1933) he was deprived of any perspectives in Germany and fled to Switzerland in the spring of 1933. His achievements as a full professor in Istanbul and as initiator of the Notgemeinschaft are remarkable in both scientific and political regards. Still, he was denied employment at the Goethe University Frankfurt. Until well after his death (1977), Philipp Schwartz's life and work received little attention in Germany. It was only after the turn of the millennium that he received the recognition he was denied during his lifetime.

[The double exclusion of the pathologist and Nazi victim Paul Kimmelstiel (1900-1970). German version]. / Die doppelte Ausgrenzung des Pathologen und NS-Opfers Paul Kimmelstiel (1900­1970).

The Hamburg pathologist Paul Kimmelstiel (1900-1970) gave his name to diabetic glomerulosclerosis (Kimmelstiel-Wilson syndrome) and thus conquered a place in the history of medicine. Far less known, however, is the fact that Kimmelstiel was one of the Jewish victims of the Third Reich. He was dismissed in 1933, saw himself forced to emigrate in 1934, and fought for "rehabilitation" ("Wiedergutmachung") after 1945.The present article focuses on Kimmelstiel's role as a politically persecuted and disenfranchised Jew.It examines (1) the background to his dismissal and forced emigration, (2) the question of "compensation" for his deprivation in postwar Germany, but also (3) the interactions between this racially motivated exclusion and biographical uprooting on one hand and the subsequent, highly remarkable international career development on the other.The study is based on previously unknown archival sources and on a reanalysis of the relevant research literature.This paper concludes that Kimmelstiel's emigration took place under traumatic circumstances. More astonishing is the fact that he quickly developed into a highly respected and famous exile scientist. However, the political and professional treatment of Kimmelstiel in post-war Germany was much less favorable. His efforts for rehabilitation were only partially successful, taking a long time and requiring considerable efforts. Only laying a Stolperstein monument in front of the University Hospital Hamburg-Eppendorf in 2014 marked a provisional, conciliatory conclusion in dealing with the victim Paul Kimmelstiel.

Induction of tumor-specific CTL responses using the C-terminal fragment of Viral protein R as cell penetrating peptide.

The discovery of tumor-associated antigens recognized by T lymphocytes opens the possibility of vaccinating cancer patients with defined antigens. However, one of the major limitation of peptide-based vaccines is the low immunogenicity of antigenic peptides. Interestingly, if these epitopes are directly delivered into the cytoplasm of antigen presenting cells, they can be efficiently presented via the direct MHC class I presentation pathway. To improve antigen entry, one promising approach is the use of cell penetrating peptides (CPPs). However, most studies use a covalent binding of the CPP with the antigen. In the present study, we focused on the C-terminal domain of Vpr which was previously demonstrated to efficiently deliver plasmid DNA into cells. We provide evidence that the peptides Vpr55-91 and Vpr55-82 possess the capacity of delivering proteins and epitopes into cell lines as well as into human primary dendritic cells, without the necessicity for a chemical linkage. Moreover, immunization of HLA-A2 transgenic mice with Vpr55-91 as the sole adjuvant is able to induce antigen-specific cytotoxic T lymphocytes against multiple tumor epitopes.