A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival and progression of tumors. Here we report cyclo-CLLFVY, identified from a library of 3.2 million cyclic hexapeptides using a genetically encoded high-throughput screening platform, as an inhibitor of the HIF-1α/HIF-1β protein-protein interaction in vitro and in cells. The identified compound inhibits HIF-1 dimerization and transcription activity by binding to the PAS-B domain of HIF-1α, reducing HIF-1-mediated hypoxia response signaling in a variety of cell lines, without affecting the function of the closely related HIF-2 isoform. The reported cyclic peptide demonstrates the utility of our high-throughput screening platform for the identification of protein-protein interaction inhibitors, and forms the starting point for the development of HIF-1 targeted cancer therapeutics

Using Fast-Steering Mirror Control to Reduce Instrument Pointing Errors Caused by Spacecraft Jitter

The scope of this study was to investigate the benefit of using feedback control of a Fast Steering Mirror (FSM) to reduce instrument pointing errors. Initially, the study identified FSM control technologies and categorized them according to their use, range of applicability, and physical requirements. Candidate payloads were then evaluated according to their relevance in use of fast steering minor control technologies. This leads to the mission and instrument selection which served as the candidate mission for numerical modeling. A standard SmallSat was designed in order to accommodate the payload requirements (weight, size, power, etc.). This included sizing the SmallSat bus, sizing the solar array, choosing appropriate antennas, and identifying an attitude control system (ACS). A feedback control system for the FSM compensation was then designed, and the instrument pointing error and SmallSat jitter environment for open-loop and closed-loop FSM control were evaluated for typical SmallSat disturbances. The results were then compared to determine the effectiveness of the FSM feedback control system

Case Report on Leiomyosarcoma of the Vulva: A Rare Pathology

Leiomyosarcoma (LMS) of the vulva is rare. However it is the most common histologic subtype of vulvar sarcoma, accounting for approximately 1% of all vulvar malignancies. [1-8] Whether genetics and epigenetics play a role in pathogenesis is unclear. [1] The tumor is slow-growing with non-specific symptoms, has high metastatic potential, and follows a bimodal age distribution. [1-8] Diagnosis and prognosis are based upon immunohistochemical expression and criteria from early literature. [1,3,5-7] The most common therapeutic approach involves radical vulvectomy with lymph node resection. The value of adjuvant chemotherapy and radiation remains unknown. [1,3,5-8] Our case describes a 46-year-old Caucasian G2P2 female with LMS of the left labia

Superhydrophobic lab-on-chip measures secretome protonation state and provides a personalized risk assessment of sporadic tumour

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual’s diagnosis and/or help clarify risk in healthy populations

Characterization of spacecraft and environmental disturbances on a SmallSat

The objective of this study is to model the on-orbit vibration environment encountered by a SmallSat. Vibration control issues are common to the Earth observing, imaging, and microgravity communities. A spacecraft may contain dozens of support systems and instruments each a potential source of vibration. The quality of payload data depends on constraining vibration so that parasitic disturbances do not affect the payload's pointing or microgravity requirement. In practice, payloads are designed incorporating existing flight hardware in many cases with nonspecific vibration performance. Thus, for the development of a payload, designers require a thorough knowledge of existing mechanical devices and their associated disturbance levels. This study evaluates a SmallSat mission and seeks to answer basic questions concerning on-orbit vibration. Payloads were considered from the Earth observing, microgravity, and imaging communities. Candidate payload requirements were matched to spacecraft bus resources of present day SmallSats. From the set of candidate payloads, the representative payload GLAS (Geoscience Laser Altimeter System) was selected. The requirements of GLAS were considered very stringent for the 150 - 500 kg class of payloads. Once the payload was selected, a generic SmallSat was designed in order to accommodate the payload requirements (weight, size, power, etc.). This study seeks to characterize the on-orbit vibration environment of a SmallSat designed for this type of mission and to determine whether a SmallSat can provide the precision pointing and jitter control required for earth observing payloads

MKIDGen3: Energy-Resolving, Single-Photon-Counting MKID Readout on an RFSoC

Building large, cryogenic MKID arrays requires processing highly-multiplexed, wideband readout signals in real time; a task that has previously required large, heavy, and power-intensive custom electronics. In this work, we present the third-generation UVOIR MKID readout system (Gen3) which is capable of reading out twice as many detectors with a fifth the weight and power and an order of magnitude less volume and cost-per-pixel as compared to the previous system. Gen3 leverages the Xilinx RFSoC4x2 platform to read out 2048, 1 MHz MKID channels per board. The system takes a modern approach to FPGA design using Vitis High-Level Synthesis (HLS) to specify signal processing blocks in C/C++, Vivado ML Intelligent Design Runs (IDR) to inform implementation stragety and close timing, and Python Productivity for ZYNQ (PYNQ) to simplify interacting with and programming the FPGA using Python. This design suite and tool flow allows general users to contribute to and maintain the design and positions Gen3 to rapidly migrate to future platforms as they become available. In this work, we describe the system requirements, design, and implementation. We also provide performance characterization details and show that the system achieves detector-limited resolving power in the case of few readout tones and minimal degradation with all 2048 tones. Planned upgrades and future work are also discussed. The Gen3 MKID readout system is fully open-source and is expected to facilitate future array scaling to megapixel-sized formats and increase the feasibility of deploying UVOIR MKIDs in space

Temperature-dependent development, cold tolerance, and potential distribution of cricotopus lebetis (Diptera: Chironomidae), a tip miner of hydrilla verticillata (Hydrocharitaceae)

© The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America. A chironomid midge, Cricotopus lebetis (Sublette) (Diptera: Chironomidae), was discovered attacking the apical meristems of Hydrilla verticillata (L.f. Royle) in Crystal River, Citrus Co., Florida in 1992. The larvae mine the stems of H. verticillata and cause basal branching and stunting of the plant. Temperature-dependent development, cold tolerance, and the potential distribution of the midge were investigated. The results of the temperature-dependent development study showed that optimal temperatures for larval development were between 20 and 30°C, and these data were used to construct a map of the potential number of generations per year of C. lebetis in Florida. Data from the cold tolerance study, in conjunction with historical weather data, were used to generate a predicted distribution of C. lebetis in the United States. A distribution was also predicted using an ecological niche modeling approach by characterizing the climate at locations where C. lebetis is known to occur and then finding other locations with similar climate. The distributions predicted using the two modeling approaches were not significantly different and suggested that much of the southeastern United States was climatically suitable for C. lebetis

Insect herbivores associated with Nymphaea mexicana (Nymphaeaceae) in southern United States: potential biological control agents for South Africa

Nymphaea mexicana Zuccarini (Nymphaeaceae) (Mexican waterlily) is an emergent floating-leaved aquatic plant from the southeastern USA that is invasive in South Africa. In invaded waterbodies this plant restricts water movement, increases siltation, decreases recreational activities, and can deplete water oxygen levels, which in turn negatively impacts aquatic fauna. Currently there are no chemical, mechanical, or biological control programs in place for N. mexicana in South Africa, but the sustainability of biological control makes this the most desirable option. Field surveys for potential biological control agents were conducted in the native range of N. mexicana in Florida, Louisiana, and Texas from Aug to Oct 2018. Leaves, stems, flowers, and roots of N. mexicana were searched for insect herbivores by hand and using Berlese funnels. Insects were prioritized for use as biological control agents by considering the extent and type of feeding damage, field host range, and incidence (percentage of sites in which each species was found). In total, 15 confirmed species were found feeding on N. mexicana, and some taxa were identified only to family level. Incidence coverage estimator mean, MMRuns, Chao 2 mean, and Chao 2 upper 95% CI species accumulation estimators predicted that between 2 and 5 species were missed during the surveys. Based on field observations, Bagous americanus LeConte (Coleoptera: Curculionidae), and Megamelus toddi Beamer (Hemiptera: Delphacidae) were prioritized. Host specificity trials will be conducted to determine whether these insects may be used as biological control agents of N. mexicana

ACTA OTORHINOLARYNGOLOGICA ITALICA

Presentiamo un caso di posizionamento di impianto cocleare in un uomo di 50 anni che, dopo aver subito tre anni prima un intervento per via retrosigmoidea per un neurinoma dellacustico in stadio 1, è stato colpito da ipoacusia improvvisa ipsilaterale sviluppando un intenso acufene. Dopo lattivazione dellimpianto lacufene è sceso da un grado 4 ad un grado 2 secondo il THI. Sono migliorate le capacità di localizzazione. Lascolto nel rumore (S/R + 7 dB) con il segnale proveniente dal lato operato è migliorato da 38 a 100%. Abbiamo inoltre verificato un significativo incremento dei punteggi relativi a spazialità e linguaggio del questionario Speech, spatial and qualities of sounds. In conclusione limpianto cocleare è una soluzione praticabile ed efficace in caso di insorgenza di ipoacusia ritardata dopo chirurgia conservativa del neurinoma dellacustico