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Microsampling of patient blood promises several benefits over conventional phlebotomy practices to facilitate precision medicine studies. These include at-home patient blood collection, supporting telehealth monitoring, minimal postcollection processing, and compatibility with nonrefrigerated transport and storage. However, for proteomic biomarker studies, mass spectrometry of whole blood has generally been avoided in favor of using plasma or serum obtained from venepuncture. We evaluated the use of a volumetric absorptive microsampling (VAMS) device as a sample preparation matrix to enable LC-MS proteomic analyses of dried whole blood. We demonstrated the detection and robust quantitation of up to 1600 proteins from single-shot shotgun-LC-MS analysis of dried whole blood, greatly enhancing proteome depth compared with conventional single-shot LC-MS analyses of undepleted plasma. Some proteins not previously reported in blood were detected using this approach. Various washing reagents were used to demonstrate that proteins can be preferentially removed from VAMS devices prior to downstream analyses. We provide a demonstration that archival frozen blood cell pellets housed under long-term storage (exceeding 5 years) are compatible with VAMS to enable quantitation of potential biomarker proteins from biobank repositories. These demonstrations are important steps in establishing viable analysis workflows to underpin large-scale precision medicine studies. Data are available via ProteomeXchange with the identifier PXD028605.

This article presents a full-duplex (FD) rake receiver (RX) that uses the orthogonality properties of pseudo-noise (PN) codes to reject transmitter (TX) self-interference (SI) in the RF domain, allowing simultaneous transmit and receive (STAR) operation in the same frequency channel. The rake RX also exploits multipath propagation in wireless channels and PN code orthogonality to gather signals across multipath components to increase the signal-to-noise ratio (SNR) while avoiding the fading effects of multipath channels. The rake RX shares a low-noise amplifier (LNA) between the three rake fingers and a high-linearity baseband (BB) section with the second-order filtering to improve the rejection with low power consumption. Measurements indicate that TX SI rejection is 41.2 dB in the RF domain with 9-dB SNR improvement in a multipath channel. The rake RX is implemented in a 45-nm RFSOI CMOS process and occupies an active area of 1.6 mm2 while consuming 45.8 mW per finger, including clock power consumption.

This article presents a CMOS-based, code-domain (CD), full-duplex (FD) transceiver operating in a link at 1 GHz. The CD FD link rejects in-band transmitter self-interference (TX SI) by more than 100 dB through a combination of pseudo-noise (PN) code orthogonality, circulator, and digital cancellation algorithms. A nonmagnetic CMOS circulator based on switched transmission lines is used as an antenna interface with >40-dB maximum rejection. Then, transmitter (TX) and receiver (RX) modulators spread the TX SI and correlate the desired RX signal in the RF domain. Orthogonality between the PN codes allows an additional >40-dB maximum rejection relaxing the FD transceiver linearity requirements. Finally, digital self-interference cancellation (SIC) eliminates any residual TX SI in the digital domain using a least mean squares (LMS) estimation for the SI channel based on a nonlinear truncated Volterra series model. The digital SIC can have almost 40 dB of rejection depending on the SI power level. An implemented FD node leverages these techniques to achieve an overall rejection that is around 104 dB bringing the TX signal from 20 dBm to the noise floor of the RX at −85 dBm.

Antigen-specific CD8+T cell accumulation in tumors is a prerequisite for effective immunotherapy, and yet, the mechanisms of lymphocyte transit remain poorly defined. We find that tumor-associated lymphatic vessels control T cell exit from tumors via the chemokine CXCL12, and intratumoral antigen encounter tunes CXCR4 expression on effector CD8+T cells. Only high affinity antigen downregulates CXCR4 and upregulates the CXCL12 decoy receptor, ACKR3, thereby reducing CXCL12 sensitivity and promoting T cell retention. A diverse repertoire of functional tumor-specific CD8+T cells exit the tumor, thereby limiting tumor control. CXCR4 inhibition and loss of lymphatic-specific CXCL12 boosts T cell retention and enhances response to therapeutic immune checkpoint blockade. Strategies that limit T cell egress, therefore, provide a new tool to boost immunotherapy response.One-Sentence SummaryLymphatic vessel-mediated, antigen-dependent CD8+T cell egress limits T cell accumulation in melanomas and impairs anti-tumor immunity.

The present study aimed to simultaneously examine the age-related, muscle-specific, sex-specific, and contractile mode-specific changes in isolated mouse skeletal muscle function and morphology across multiple ages. Measurements of mammalian muscle morphology, isometric force and stress (force/cross-sectional area), absolute and normalized (power/muscle mass) work-loop power across a range of contractile velocities, fatigue resistance, and myosin heavy chain (MHC) isoform concentration were measured in 232 isolated mouse (CD-1) soleus, extensor digitorum longus (EDL), and diaphragm from male and female animals aged 3, 10, 30, 52, and 78 wk. Aging resulted in increased body mass and increased soleus and EDL muscle mass, with atrophy only present for female EDL by 78 wk despite no change in MHC isoform concentration. Absolute force and power output increased up to 52 wk and to a higher level for males. A 23–36% loss of isometric stress exceeded the 14–27% loss of power normalized to muscle mass between 10 wk and 52 wk, although the loss of normalized power between 52 and 78 wk continued without further changes in stress ( P > 0.23). Males had lower power normalized to muscle mass than females by 78 wk, with the greatest decline observed for male soleus. Aging did not cause a shift toward slower contractile characteristics, with reduced fatigue resistance observed in male EDL and female diaphragm. Our findings show that the loss of muscle quality precedes the loss of absolute performance as CD-1 mice age, with the greatest effect seen in male soleus, and in most instances without muscle atrophy or an alteration in MHC isoforms.

Code-domain signal processing techniques implemented at radio frequencies (RFs) enable simultaneous transmit and receive (STAR) applications. With direct sequence spread spectrum (DSSS) techniques and RF correlators, transmit (TX) self-interference (SI) is separated from the receive (RX) signal at the antenna interface for STAR. The processing gain inherent in the code-domain approach increases the TX SI rejection in the RF domain to relax filtering and linearity requirements of the RX. A code-domain RX demonstrates 52 dB of TX SI rejection with TX code-notch and RX code-pass filters operating at the same center frequency. The RX is tunable from 0.25 to 1.25 GHz and has a gain of 39 dB at 1 GHz while consuming 90 mW of which 40 mW are consumed in the front-end filters. The RX is implemented in a 45-nm CMOS SOI process and full-duplex operation is verified through an over-the-air demonstration.

This article demonstrates a signal processing technique for receiving non-contiguous RF channels by concurrently mixing several RF bands to adjacent IF channels. Consequently, channel selection does not require local oscillator tuning and the proposed receiver (RX) can switch channels in less than 25 ns. The RX chip operates over a frequency range of 100 MHz–1.4 GHz and demonstrates an out-of-band rejection of 49 dB and a measured RX sensitivity of −86 dBm, which is the lowest measured for $N$ -path-based RXs. The chip was fabricated in a 45-nm RF silicon-on-insulator (SOI) CMOS process and occupies an active area of 0.55 mm2 with the power consumption of 23.1 mW when operating at 1 GHz. The chip performance is verified with over-the-air measurement of two transmitted signals 80 MHz apart that are received simultaneously with a 10-MHz analog-to-digital converter (ADC) at an error vector magnitude (EVM) around −20 dB. The measured dynamic range for EVM less than −20 dB is better than 86 dB for a QPSK constellation.

This letter presents a tunable notch filter that can be reconfigured to improve rejection while offering high power handling. The notch filter uses a series $N$ -path filter in conjunction with an impedance-transformed shunt $N$ -path filter to improve the transmit (TX) rejection or notch concurrent bands. A 4th-order notch provides >40-dB rejection for a single TX channel. In the dual-notch mode, the notches can be tuned to two different TX channels. Finally, a low-power single-notch mode provides >20-dB rejection with low power consumption. The filter is implemented in a 45-nm CMOS SOI process and consumes between 11.9 and 43.9 mW at 1-V supply across a tuning range from 0.45 to 0.9 GHz while providing a peak rejection >50 dB and $P_{1~{\mathrm{ dB}}}$ as high as 15.8 dBm.

Myosin motors in resting muscle are inactivated by folding against the backbone of the myosin filament in an ordered helical array and must be released from that conformation to engage in force generation. Time-resolved X-ray diffraction from single fibres of amphibian muscle showed that myosin filament activation could be inhibited by imposing unloaded shortening at the start of stimulation, suggesting that filaments were activated by mechanical stress. Here we improved the signal-to-noise ratio of that approach using whole extensor digitorum longus muscles of the mouse contracting tetanically at 28°C. Changes in X-ray signals associated with myosin filament activation, including the decrease in the first-order myosin layer line associated with the helical motor array, increase in the spacing of a myosin-based reflection associated with packing of myosin tails in the filament backbone, and increase in the ratio of the 1,1 and 1,0 equatorial reflections associated with movement of motors away from the backbone, were delayed by imposing 10-ms unloaded shortening at the start of stimulation. These results show that myosin filaments are predominantly activated by filament stress, as in amphibian muscle. However, a small component of filament activation at zero load was detected, implying an independent mechanism of partial filament activation. X-ray interference measurements indicated a switch-like change in myosin motor conformation at the start of force development, accompanied by transient disordering of motors in the regions of the myosin filament near its midpoint, suggesting that filament zonal dynamics also play a role in its activation. KEY POINTS: Activation of myosin filaments in extensor digitorum longus muscles of the mouse is delayed by imposing rapid shortening from the start of stimulation. Stress is the major mechanism of myosin filament activation in these muscles, but there is a small component of filament activation during electrical stimulation at zero stress. Myosin motors switch rapidly from the folded inhibited conformation to the actin-attached force-generating conformation early in force development.

BACKGROUND Treatment-related toxicity is common in patients with glioblastoma (GBM) receiving chemotherapy and radiotherapy (RT). Temporalis muscle thickness (TMT) is a biomarker associated with sarcopenia and worse clinical outcomes in GBM, however its relation to treatment toxicity is less studied. We hypothesize that TMT may predict toxicity and survival in GBM patients. METHODS We reviewed consecutive patients with IDH-wildtype GBM treated from 2014-2019 at a single academic center. TMT was retrospectively assessed on T1-weighted MRI scans and dichotomized based upon previously validated sex-specific cutoff values. TMT was measured on baseline MRI scan at time of diagnosis. Cox regression multivariable analysis (MVA) was used to assess survival. RESULTS We evaluated 351 patients with median age of 60y (range 20-94) and median follow-up of 14mo. Most patients were male (59%), baseline KPS >70 (95%), and MGMT unmethylated (55%). After maximal safe resection, most patients received standard (90%) or hypofractionated (10%) RT with concurrent systemic therapy (89%). On MVA, baseline low TMT (HR 1.93, p=0.01), age >65y, baseline KPS, and MGMT-unmethylated status were associated with worse OS. On MVA, baseline low TMT (HR 1.95, p=0.01), age >65y, MGMT-unmethylated status, and discontinuing systemic therapy were associated with worse profession-free survival (PFS). 21 patients did not complete anticipated treatment course of chemoradiation and adjuvant systemic therapy due to toxicity, primarily thrombocytopenia, associated with worse OS on MVA (HR 1.99, p< 0.01). Low TMT was associated with higher risk of stopping treatment due to adverse events (OR 5.25, p< 0.01) independent of age, sex, extent of resection, RT dose on MVA. CONCLUSION Baseline low TMT was associated with worse PFS and OS, and it was associated with treatment interruption due to treatment toxicity in GBM patients. While further validation is needed, TMT may help identify patients who will benefit from aggressive symptom management or treatment deintensification.

This article reports signal processing and circuit techniques for direct RF signal modulation. A pulse-encoded transition (PET) technique is introduced to reduce undesired harmonic distortion (HD) and adjacent channel leakage ratio (ACLR) generated by the direct RF modulation. To enable PET RF switching, two variations of a high-power, stacked-FET switch modulator, an 8- and 12-device stack, are designed in 45-nm silicon on insulator (SOI) CMOS. The switch design uses a tapering design to significantly improve power handling with minimal impact to switching speed. The modulators have $P_{1\,{\mathrm{ dB}}} $ values between 34 and 39 dBm while demonstrating a modulation bandwidth of nearly 500 MHz with a 1-GHz carrier. The input referred third order intercept point (IIP3) is between 46 and 61 dBm. Additionally, ACLR measurements of up to −50 dBc are demonstrated using the proposed PET technique at 30-dBm output power. To the best of our knowledge, this is record power handling and ACLR for a CMOS switch.

This paper demonstrates generalized code-selective filters for code-pass and code-reject signal processing at RF. A code-reject scheme using a quarter-wave ( $\lambda /4$ ) impedance transformation is also demonstrated to overcome tradeoffs of insertion loss (IL) and linearity compared to series band-reject $N$ -path filters. A 45-nm CMOS SOI implementation consumes a power of 9.32 mW from 1 to 1.8-V supplies at the frequency of 0.35–1.1 GHz and the chip area is 1.73 mm2. The measured transmit rejection is up to 22.6 dB with 4-dB IL. The in-band third-order-intercept point (IIP3) is up to 22.6 dBm and noise figure (NF) of 4–6 dB depending on the applied codes.

This paper presents a passive tunable matching network for load-modulation of a power amplifier (PA). With a set of discrete RF switches, different real impedance transformations can be realized to optimize the loadline match of the PA for output power and/or efficiency. To handle high-power, a 40-nm GaN MMIC process was used to realize three RF switches that switch across a ring impedance network. The tunable matching network realizes 15, 50, or 80Ω depending on the switch state with insertion loss (IL) between 1.7 and 3.3 dB at a center frequency of 28 GHz. The GaN devices have a high breakdown point and therefore the network P 1 dB exceeds 33 dBm. The bandwidth of the network exceeds 2.5 GHz.

Males exhibit higher incidence and worse prognosis for the majority of cancers, including glioblastoma (GBM). Disparate survival may be related to sex-biased responses to treatment, including radiation. Using a mouse model of GBM, we show that female cells are more sensitive to radiation, and that senescence represents a major component of the radiation therapeutic response in both sexes. Correlation analyses revealed that the CDK inhibitor p21 and irradiation induced senescence were differentially regulated between male and female cells. Indeed, female cellular senescence was more sensitive to changes in p21 levels, a finding that was observed in both wildtype and transformed murine astrocytes and patient-derived GBM cell lines. Using a novel Four Core Genotypes model of GBM, we further show that sex differences in p21-induced senescence are patterned by gonadal sex. These data suggest that sex differences in p21 induced senescence contribute to the female survival advantage in GBM.

Obesity is a global epidemic and coupled with the unprecedented growth of the world’s older adult population, a growing number of individuals are both old and obese. Whilst both ageing and obesity are associated with an increased prevalence of chronic health conditions and a substantial economic burden, evidence suggests that the coincident effects exacerbate negative health outcomes. A significant contributor to such detrimental effects may be the reduction in the contractile performance of skeletal muscle, given that poor muscle function is related to chronic disease, poor quality of life and all-cause mortality. Whilst the effects of ageing and obesity independently on skeletal muscle function have been investigated, the combined effects are yet to be thoroughly explored. Given the importance of skeletal muscle to whole-body health and physical function, the present study sought to provide a review of the literature to: (1) summarise the effect of obesity on the age-induced reduction in skeletal muscle contractile function; (2) understand whether obesity effects on skeletal muscle are similar in young and old muscle; (3) consider the consequences of these changes to whole-body functional performance; (4) outline important future work along with the potential for targeted intervention strategies to mitigate potential detrimental effects.

This paper presents a 3-finger rake receiver (RX) that exploits multipath characteristics in PN-modulated received signals to improve the signal-to-noise ratio (SNR) in full-duplex (FD) links. Orthogonality between PN codes allows up to 41.2 dB of TX self-interference (TX-SI) rejection and autocorrelation between delayed versions of received PN code improves the SNR by 9 dB. The receiver is implemented in 45-nm SOI CMOS and is tunable from 0.4 to 1.4 GHz with 30.5 dB of gain and an in-band/out-of-band baseband IIP3 of -6.5/14.2 dBm while consuming 45.8 mW per finger.

This paper describes a full-duplex (FD) radio transceiver that uses CMOS RFICs to realize high power handling and linearity. A high-rejection, magnetic-less CMOS circulator at the antenna along with high-rejection, blocker-tolerant RF code-domain correlators achieve high transmitter (TX) rejection in the RF domain. Code-domain operation supports higher linearity in FD applications. Digital cancellation increases the rejection down to noise floor of a software-defined radio (SDR). We compare the role of antenna impedance in the performance of SI rejection. The measured results demonstrate more than 104 dB TX self-interference (TX-SI) rejection at 20 dBm TX power. To the best of our knowledge, this work presents the best reported TX-SI rejection at more than 20 dBm.

Exhibition Review: Last Supper in Pompeii - too much death not enough food

Prolonged high-fat diets (HFDs) can cause intramyocellular lipid (IMCL) accumulation that may negatively affect muscle function. We investigated the duration of a HFD required to instigate these changes, and whether the effects are muscle specific and aggravated in older age. Muscle morphology was determined in the soleus, extensor digitorum longus (EDL) and diaphragm muscles of female CD-1 mice from 5 groups: young fed a HFD for 8 weeks (YS-HFD, n=16), young fed a HFD for 16 weeks (YL-HFD, n=28) and young control (Y-Con, n=28). The young animals were 20 weeks old at the end of the experiment. Old (70 weeks) female CD-1 mice received either a normal diet (O-Con, n=30) or a HFD for 9 weeks (OS-HFD, n=30). Body mass, body mass index and intramyocellular lipid (IMCL) content increased in OS-HFD (P≤0.003). In the young mice, this increase was seen in YL-HFD and not YS-HFD (P≤0.006). The soleus and diaphragm fibre cross-sectional area (FCSA) in YL-HFD was larger than that in Y-Con (P≤0.004) while OS-HFD had a larger soleus FCSA compared with that of O-Con after only 9 weeks on a HFD (P, Summary: High-fat diet induces muscle fibre hypertrophy, an increase in oxidative capacity and accumulation of intracellular lipids, earlier in old than in young mice; these adaptations are muscle specific with the EDL being least responsive.

CMOS RF switches support watt-level RF output power while enabling signal processing with high speed. Typically, RF FET switches offer a tradeoff between a power handling and modulation bandwidth. This paper investigates the cause of compression in a FET switch, and the analysis suggests the optimization of the gate driving impedance for a stacked-FET switch. A design methodology is presented to realize watt-level power handling with high fractional bandwidth (FBW). The measurements demonstrate a BPSK modulator that can handle up to 10 W with wide FBW. The high-power, low-insertion loss, and high-modulation bandwidth demonstrate record performance.

Recent evidence has demonstrated an obesity-induced, skeletal muscle-specific reduction in contractile performance. The extent and magnitude of these changes in relation to total dose of high-fat diet consumption remains unclear. This study aimed to examine the dose–response relationship between a high-fat diet and isolated skeletal muscle contractility. 120 female CD1 mice were randomly assigned to either control group or groups receiving 2, 4, 8 or 12 weeks of a high-calorie diet (N = 24). At 20 weeks, soleus, EDL or diaphragm muscle was isolated (n = 8 in each case) and isometric force, work loop power output and fatigue resistance were measured. When analysed with respect to feeding duration, there was no effect of diet on the measured parameters prior to 8 weeks of feeding. Compared to controls, 8-week feeding caused a reduction in normalised power of the soleus, and 8- and 12-week feeding caused reduced normalised isometric force, power and fatigue resistance of the EDL. Diaphragm from the 12-week group produced lower normalised power, whereas 8- and 12-week groups produced significantly lower normalised isometric force. Correlation statistics indicated that body fat accumulation and decline in contractility will be specific to the individual and independent of the feeding duration. The data indicate that a high-fat diet causes a decline in muscle quality with specific contractile parameters being affected in each muscle. We also uniquely demonstrate that the amount of fat gain, irrespective of feeding duration, may be the main factor in reducing contractile performance.

A series code selective filter (CSF) for full-duplex communication is presented. The CSF passes a desired signal in a frequency band only when the signal is tagged with a pseudonoise (PN) code that matches the code at the filter. This approach is shown to reject a transmit signal in the same band as a desired receive signal. The coded transmitter signal is orthogonal through appropriate code selection from a codebook and the PN sequence spreads the signal energy outside the filter bandwidth (BW). The CSF achieves a self-interference rejection of 23.2 dB over a 10-MHz BW using on-chip generated Walsh codes. The CSF operates from 300 to 675 MHz and consumes 28.2 mA from a 1-V supply at 500 MHz. The CSF achieves an IIP3 of 15.7 dBm. The CSF was implemented in a 45-nm CMOS silicon on insulator process and occupies an area of 0.9 mm2.

There is currently a limited amount of literature investigating the age-related changes in eccentric muscle function in vitro. The present study uniquely uses the work loop (WL) technique, to better replicate in vivo muscle function, in the assessment of the age- and muscle-specific changes in acute and sustained concentric and eccentric power and recovery. Whole soleus or extensor digitorum longus (EDL) muscles were isolated from 10-week and 78-week-old mice and acute and sustained concentric and eccentric WL power assessed. Despite an age-related increase in body and muscle mass, peak absolute power for both muscles was unaffected by age. Peak concentric power normalized to muscle mass declined significantly for each muscle, while peak normalized eccentric power declined only for soleus. Fatigue resistance and recovery for the soleus did not differ between age or contraction type. Older EDL was less resistant to concentric fatigue, but was better able to withstand sustained eccentric activity than young EDL. We have shown that age-related changes in muscle quality are more limited for eccentric function than concentric function. A greater bodily inertia is likely to further reduce in vivo locomotor performance in older animals.

Obesity affects the major metabolic and cellular processes involved in skeletal muscle contractility. Surprisingly, the effect of obesity on isolated skeletal muscle performance remains unresolved. The present study is the first to examine the muscle-specific changes in contractility following dietary-induced obesity using an isolated muscle work-loop (WL) model that more closely represents in vivo muscle performance. Following 16-wk high-calorific feeding, soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) were isolated from female (CD-1) mice, and contractile performance was compared against a lean control group. Obese SOL produced greater isometric force; however, isometric stress (force per unit muscle area), absolute WL power, and normalized WL power (watts per kilogram muscle mass) were unaffected. Maximal isometric force and absolute WL power of the EDL were similar between groups. For both EDL and DIA, isometric stress and normalized WL power were reduced in the obese groups. Obesity caused a significant reduction in fatigue resistance in all cases. Our findings demonstrate a muscle-specific reduction in contractile performance and muscle quality that is likely related to in vivo mechanical role, fiber type, and metabolic profile, which may in part be related to changes in myosin heavy chain expression and AMP-activated protein kinase activity. These results infer that, beyond the additional requirement of moving a larger body mass, functional performance and quality of life may be further limited by poor muscle function in obese individuals. As such, a reduction in muscle performance may be a substantial contributor to the negative cycle of obesity.NEW & NOTEWORTHY The effect of obesity on isolated muscle function is surprisingly underresearched. The present study is the first to examine the effects of obesity on isolated muscle performance using a method that more closely represents real-world muscle function. This work uniquely establishes a muscle-specific profile of mechanical changes in relation to underpinning mechanisms. These findings may be important to understanding the negative cycle of obesity and in designing interventions for improving weight status.

Sex differences in the rates of glioblastoma increase with age. There are likely to be multiple biological mechanisms underlying these sex differences. Here, we focused on the changes that occur with aging in the secretomes of male and female astrocytes to determine whether sex differences in chemokine and cytokine secretion, and inflammatory cell recruitment, could be one of those mechanisms. We focused on glioblastoma (GBM) and the role that senescent astrocytes might play in the age-dependent widening of the gap between male and female GBM cases. We found that the senescence associated secretory phenotype of male and female astrocytes significantly differed, notably in the enrichment of Fractalkine (1.33:1 (F:M)), the primary chemoattractant for microglia, in female compared to male SASP. This was in contrast to the greater abundance of tumorigenic growth factors like bFGF (1.25:1 (M:F)), in the male SASP. Implantation of either male or female senescent astrocytes into the brains of mice resulted in the recruitment of microglia to the injection site. Regardless of the recipient mouse sex, female astrocyte implantation resulted in significantly larger microglial infiltrates (2-fold) and greater astrocyte activation, as compared to the injection of equal numbers of male senescent cells. We propose a model for how sex differences in astrocyte SASP could result in lower rates of GBM with age in females: greater microglial attraction to senescent cells results in their enhanced clearance and consequently a reduction in senescence-associated GBM promotion.

Incidence rates for glioblastoma increase exponentially with age in a sex-specific manner, with a steeper increase observed in men. This suggests that age may be a more significant factor in promoting male tumors than female tumors. Drivers in the age-related cancer increase include both the accumulation of DNA damage and microenvironment changes, specifically an increase in the number of senescent cells. Cellular senescence comprises two distinct components – a cell cycle arrest program that prevents proliferation of mutated cells and acts as a potent anti-cancer mechanism, and a paracrine signaling component that can have both pro- and anti-tumorigenic properties. The contribution of senescence to brain tumor incidence and outcome is currently unknown; additionally, no research has been done on whether there are sex differences in mechanisms of senescence induction or in the secretory phenotype of senescent cells. Using both wildtype astrocytes and a glioblastoma model, we show that female cells have a lower threshold for senescence induction in response to oxidative stress, telomere shortening, and DNA damage, and that sex differences in senescence induction in response to DNA damage are in part mediated by differences in the regulation of p21. In addition, we show that male and female senescent astrocytes differ in their secretory phenotypes. Male senescent astrocytes secrete more tumor promoting factors, and conditioned media from male but not female senescent astrocytes promotes tumor cell proliferation. These findings provide a potential explanation for sex differences in glioblastoma incidence rates. Achieving a better understanding of mechanisms of senescence and how they differ in male and female cells could advance development of senescence directed therapies and potentially improve cancer treatment for a range of tumor types.

This paper demonstrates a code-domain transceiver that incorporates a transmit (TX) modulator and receive (RX) RF signal correlator. We propose a transmission gate switch with 12.1-dBm/23.1-dBm P1dB/IIP3 for both RF correlation and filtering and rejects TX self-interference by 49.5 dB. An integrate-and-dump N-path filter improves rejection by 8 dB. The RX power consumption is 18 mW at 1 GHz. The TX modulator operates to RF power levels up to 34.3 dBm and consumes less than 40 mW for 300 Megachip-per-second (Mc/s). Over the air testing demonstrates synchronization with Barker codes.