R&D Contracts in the Soviet Union

As the Soviet economy recovered from WWII devastation, economic officials struggled to design better incentives for promoting rapid technological progress in industry. They created model contracts for R&D work hoping to improve Soviet industry's relatively mediocre performance in using new technologies. This article describes the problems encountered in making model R&D contracts into an effective tool for promoting industrial innovation in the USSR. At the same time model R&D contracts were being established, a more radical reform, a "socialist license," was proposed by an official at the Soviet patent office (State Committee for Inventions and Discoveries), an agency whose top management came from the military-industrial complex. These proposed licenses gave R&D organizations greater financial benefits from new technologies by allowing licensing fees that related to cost savings and quality improvements. Economic officials, however, rejected the reform, viewing it as a challenge to the Communist Party's central planning authority. R&D contracts succeeded primarily in the educational ministry (MinVuz) and Academy of Sciences institutes, linking them more closely to industry, especially to facilities in the military-industrial complex.Während des Wiederaufbaus der UdSSR-Wirtschaft nach dem Zweitem Weltkrieg bemühten sich die sowjetischen Wirtschaftsfunktionäre, bessere Anreize durchzuführen um das Tempo des technologischen Fortschritts bei der Industrie zu erhöhen. Sie führten deshalb Musterverträge für Forschung und Entwicklungsarbeit ein mit der Hoffnung, die relativ mittelmäßige Leistung der Benutzung neuer Technologie in der UdSSR zu verbessern. Der folgende Artikel beschreibt die Musterverträge für Forschung und Entwicklungsarbeit und die Schwierigkeiten die sie begegneten während der Versuche, sie als Instrument der Verbesserung der industriellen Innovation einzuleiten. Während der Entwicklung dieser neuen Verträge erschien plötzlich eine radikaler Reformsvorschlag, eine sogenannte "sozialistische Lizenz". Sie kamen von einem Beamten beim sowjetischen Patentbüro (Staatskomitee für Erfindungen und Entdeckungen) das viele Spitzenmanager in der Rüstungsindustrie hervorbrachte. Mit der Aussicht auf eine sozialistische Lizenz, konnten Forschungs- und Entwicklungsorganisationen mehr von ihren neuen Technologien profitieren und ihre Lizenzgebühren auf Kostenersparnisse und Qualitätsverbesserungen zielen. Die Wirtschaftsbeamten erhoben einen heftigen Widerspruch dagegen, denn sie sahen diesen Vorschlag als gegen die zentrale Planlenkung gerichtet. Die neuen Forschungs- und Entwicklungsverträge hatten ihren größten Erfolg beim Erziehungsministerium (Minvuz) und bei den Instituten der Akademie der Wissenschaften und sie haben ihre Organisationen enger mit der Industrie verknüpft, besonders mit der Rüstungsindustrie

Carrier-envelope phase stability of hollow-fibers used for high-energy, few-cycle pulse generation

We investigated the carrier-envelope phase (CEP) stability of a hollow-fiber setup used for high-energy, few-cycle pulse generation. Saturation of the output pulse energy is observed at 0.6 mJ for a 260 um inner-diameter, 1 m long fiber, statically filled with neon, with the pressure adjusted to achieve an output spectrum capable of supporting sub-4fs pulses. The maximum output pulse energy can be increased to 0.8mJ by using either differential pumping, or circularly polarized input pulses. We observe the onset of an ionization-induced CEP instability, which does not increase beyond an input pulse energy of 1.25 mJ due to losses in the fiber caused by ionization. There is no significant difference in the CEP stability with differential pumping compared to static-fill, demonstrating that gas flow in differentially pumped fibers does not degrade the CEP stabilization.Comment: 4 pages, 4 figure

ESR1 mutations: Moving towards guiding treatment decision-making in metastatic breast cancer patients

Mutations in the gene coding for the estrogen receptor (ER), ESR1, have been associated with acquired endocrine resistance in patients with ER-positive metastatic breast cancer (MBC). Functional studies revealed that these ESR1 mutations lead to constitutive activity of the ER, meaning that the receptor is active in absence of its ligand estrogen, conferring resistance against several endocrine agents. While recent clinical studies reported that the occurrence of ESR1 mutations is rare in primary breast cancer tumors, these mutations are more frequently observed in metastatic tissue and circulating cell-free DNA of MBC patients pretreated with endocrine therapy. Given the assumed impact that the presence of ESR1 mutations has on outcome to endocrine therapy, assessing ESR1 mutations in MBC patients is likely to be of significant interest to further individualize treatment for MBC patients. Here, ESR1 mutation detection methods and the most relevant pre-clinical and clinical studies on ESR1 mutations regarding endocrine resistance are reviewed, with particular interest in the ultimate goal of guiding treatment decision-making based on ESR1 mutations

Expression of hypoxia-induced proteins in ductal carcinoma in situ and invasive cancer of the male breast

AIMS: The aim of this study was to determine the role of hypoxia in male breast carcinogenesis by evaluating the expression of the hypoxia-related proteins, hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase IX (CAIX) and glucose transporter-1 (Glut-1), in ductal carcinoma in situ (DCIS) of the male breast in relation to invasive cancer (IC). METHODS: Tumour tissue blocks of 18 cases of pure DCIS, 58 DCIS cases adjacent to IC (DCIS-AIC) and the 58 IC cases were stained by immunohistochemistry for HIF-1α, CAIX and Glut-1, and expression frequencies and patterns (diffuse and/or perinecrotic) were noted. RESULTS: HIF-1α overexpression was observed in 61.1% (11/18) of pure DCIS, in 37.9% (22/58) of DCIS-AIC and in 36.2% (21/58) of IC cases (not significant (n.s.)). CAIX overexpression was observed in 16.7% (3/18) of pure DCIS, in 37.9% (22/58) of DCIS-AIC and in 24.1% (14/58) of IC cases (n.s.). Glut-1 overexpression was observed in 61.1% (11/18) of pure DCIS, in 75.9% (44/58) of DCIS-AIC and in 62.1% (36/58) of IC cases (n.s.). Expression of hypoxia-related proteins was seen around necrosis in a little over one-third of DCIS cases, and often coincided with expression in adjacent IC when present. All these observations indicate that the hypoxia response is already at its maximum in the preinvasive DCIS stage. CONCLUSIONS: In conclusion, male DCIS frequently shows activated hypoxia response, comparable to male IC. This indicates that the activated hypoxia response previously seen in male IC is not a late bystander but likely a genuine carcinogenetic event

Elucidating the underlying functional mechanisms of breast cancer susceptibility through post-GWAS analyses

Genome-wide association studies (GWAS) have identified more than 170 single nucleotide polymorphisms (SNPs) associated with the susceptibility to breast cancer. Together, these SNPs explain 18% of the familial relative risk, which is estimated to be nearly half of the total familial breast cancer risk that is collectively explained by low-risk susceptibility alleles. An important aspect of this success has been the access to large sample sizes through collaborative efforts within the Breast Cancer Association Consortium (BCAC), but also collaborations between cancer association consortia. Despite these achievements, however, understanding of each variant's underlying mechanism and how these SNPs predispose women to breast cancer remains limited and represents a major challenge in the field, particularly since the vast majority of the GWAS-identified SNPs are located in non-coding regions of the genome and are merely tags for the causal variants. In recent years, fine-scale mapping studies followed by functional evaluation of putative causal variants have begun to elucidate the biological function of several GWAS-identified variants. In this review, we discuss the findings and lessons learned from these post-GWAS analyses of 22 risk loci. Identifying the true causal variants underlying breast cancer s

Increased MAPK1/3 Phosphorylation in Luminal Breast Cancer Related with PIK3CA Hotspot Mutations and Prognosis

INTRODUCTION: While mutations in PIK3CA are most frequently (45%) detected in luminal breast cancer, downstream PI3K/AKT/mTOR pathway activation is predominantly observed in the basal subtype. The aim was to identify proteins activated in PIK3CA mutated luminal breast cancer and the clinical relevance of such a protein in breast cancer patients. MATERIALS AND METHODS: Expression levels of 171 signaling pathway (phospho-)proteins established by The Cancer Genome Atlas (TCGA) using reverse phase protein arrays (RPPA) were in silico examined in 361 breast cancers for their relation with PIK3CA status. MAPK1/3 phosphorylation was evaluated with immunohistochemistry on tissue microarrays (TMA) containing 721 primary breast cancer core biopsies to explore the relationship with metastasis-free survival. RESULTS: In silico analyses revealed increased phosphorylation of MAPK1/3, p38 and YAP, and decreased expression of p70S6K and 4E–BP1 in PIK3CA mutated compared to wild-type luminal breast cancer. Augmented MAPK1/3 phosphorylation was most significant, i.e. in luminal A for both PIK3CA exon 9 and 20 mutations and in luminal B for exon 9 mutations. In 290 adjuvant systemic therapy naïve lymph node negative (LNN) breast cancer patients with luminal cancer, high MAPK phosphorylation in nuclei (HR = 0.49; 95% CI, 0.25–0.95; P =.036) and in tumor cells (HR = 0.37; 95% CI, 0.18–0.79; P =.010) was related with favorable metastasis-free survival in multivariate analyses including traditional prognostic factors. CONCLUSION: Enhanced MAPK1/3 phosphorylation in luminal breast cancer is related to PIK3CA exon-specific mutations and correlated with favorable prognosis especially when located in the nuclei of tumor cells

Subject-controlled, on demand, dorsal genital nerve stimulation to treat urgency urinary incontinence:a pilot

Contains fulltext : 171558.pdf (publisher's version ) (Open Access)OBJECTIVES: To evaluate the effect of subject-controlled, on-demand, dorsal genital nerve (DGN) stimulation on non-neurogenic urgency urinary incontinence (UUI) in a domestic setting. MATERIALS AND METHODS: Non-neurogenic patients >18 years with overactive bladder symptoms and UUI were included. Exclusion criteria were mainly stress urinary incontinence. Patients underwent 1 week of subject-controlled, on-demand, DGN stimulation, delivered by a percutaneously placed electrode near the DGN connected to an external stimulator (pulse-rate 20 Hz, pulse-width 300 mus). Patients activated the stimulator when feeling the urge to void and stimulated for 30 s. The amplitude was set at the highest tolerable level. A bladder diary including a severity score of the UUI episodes/void (scores: 0 = none, 1 = drops, 2 = dashes, 3 = soaks) and a padtest was kept 3 days prior to, during, and 3 days after the test period. The subjective improvement was also scored. RESULTS: Seven patients (4 males/3 females) were enrolled, the mean age was 55 years (range 23-73). Six completed the test week. In the remaining patient the electrode migrated and was removed. 5/6 finalized the complete bladder diary, 1/6 recorded only the heavy incontinence episodes (score = 3). 4/6 completed the padtest. In all patients who finalized the bladder diary the number of UUI episodes decreased, in 3/5 with >/=60%. The heavy incontinence episodes (score = 3) were resolved in 2/6 patients, and improved >/=80% in the other 4. The severity score of the UUI episodes/void was improved with >/= 60% in 3/5 patients. The mean subjective improvement was 73%. CONCLUSION: This feasibility study indicates that subject-controlled, on-demand DGN stimulation using a percutaneously placed electrode is possible over a longer time period, in a home setting, with a positive effect on non-neurogenic overactive bladder symptoms with UUI. Although the placement is an easy procedure, it is difficult to fixate the electrode to keep it in the correct position. Improvements in hardware, like a better fixated electrode and an easy to control stimulator, are necessary to make SODGNS a treatment possibility in the future