Exotic Dark Matter Search with the Majorana Demonstrator.

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.

Final Result of the Majorana Demonstrator's Search for Neutrinoless Double-ß Decay in

The Majorana Demonstrator searched for neutrinoless double-ß decay (0νßß) of ^{76}Ge using modular arrays of high-purity Ge detectors operated in vacuum cryostats in a low-background shield. The arrays operated with up to 40.4 kg of detectors (27.2 kg enriched to ∼88% in ^{76}Ge). From these measurements, the Demonstrator has accumulated 64.5 kg yr of enriched active exposure. With a world-leading energy resolution of 2.52 keV FWHM at the 2039 keV Q_{ßß} (0.12%), we set a half-life limit of 0νßß in ^{76}Ge at T_{1/2}>8.3×10^{25} yr (90% C.L.). This provides a range of upper limits on m_{ßß} of (113-269) meV (90% C.L.), depending on the choice of nuclear matrix elements.

Erratum: Search for Spontaneous Radiation from Wave Function Collapse in the Majorana Demonstrator [Phys. Rev. Lett. 129, 080401 (2022)].

This corrects the article DOI: 10.1103/PhysRevLett.129.080401.

Constraints on the Decay of

^{180m}Ta is a rare nuclear isomer whose decay has never been observed. Its remarkably long lifetime surpasses the half-lives of all other known ß and electron capture decays due to the large K-spin differences and small energy differences between the isomeric and lower-energy states. Detecting its decay presents a significant experimental challenge but could shed light on neutrino-induced nucleosynthesis mechanisms, the nature of dark matter, and K-spin violation. For this study, we repurposed the Majorana Demonstrator, an experimental search for the neutrinoless double-beta decay of ^{76}Ge using an array of high-purity germanium detectors, to search for the decay of ^{180m}Ta. More than 17 kg, the largest amount of tantalum metal ever used for such a search, was installed within the ultralow-background detector array. In this Letter, we present results from the first year of Ta data taking and provide an updated limit for the ^{180m}Ta half-life on the different decay channels. With new limits up to 1.5×10^{19} yr, we improved existing limits by 1-2 orders of magnitude which are the most sensitive searches for a single ß and electron capture decay ever achieved. Over all channels, the decay can be excluded for T_{1/2}<0.29×10^{18} yr.

Search for Spontaneous Radiation from Wave Function Collapse in the Majorana Demonstrator.

The Majorana Demonstrator neutrinoless double-beta decay experiment comprises a 44 kg (30 kg enriched in ^{76}Ge) array of p-type, point-contact germanium detectors. With its unprecedented energy resolution and ultralow backgrounds, Majorana also searches for rare event signatures from beyond standard model physics in the low energy region below 100 keV. In this Letter, we test the continuous spontaneous localization (CSL) model, one of the mathematically well-motivated wave function collapse models aimed at solving the long-standing unresolved quantum mechanical measurement problem. While the CSL predicts the existence of a detectable radiation signature in the x-ray domain, we find no evidence of such radiation in the 19-100 keV range in a 37.5 kg-y enriched germanium exposure collected between December 31, 2015, and November 27, 2019, with the Demonstrator. We explored both the non-mass-proportional (n-m-p) and the mass-proportional (m-p) versions of the CSL with two different assumptions: that only the quasifree electrons can emit the x-ray radiation and that the nucleus can coherently emit an amplified radiation. In all cases, we set the most stringent upper limit to date for the white CSL model on the collapse rate, λ, providing a factor of 40-100 improvement in sensitivity over comparable searches. Our limit is the most stringent for large parts of the allowed parameter space. If the result is interpreted in terms of the Diòsi-Penrose gravitational wave function collapse model, the lower bound with a 95% confidence level is almost an order of magnitude improvement over the previous best limit.

Search for Solar Axions via Axion-Photon Coupling with the Majorana Demonstrator.

Axions were originally proposed to explain the strong-CP problem in QCD. Through axion-photon coupling, the Sun could be a major source of axions, which could be measured in solid state detection experiments with enhancements due to coherent Primakoff-Bragg scattering. The Majorana Demonstrator experiment has searched for solar axions with a set of ^{76}Ge-enriched high purity germanium detectors using a 33 kg-yr exposure collected between January, 2017 and November, 2019. A temporal-energy analysis gives a new limit on the axion-photon coupling as g_{aγ}<1.45×10^{-9} GeV^{-1} (95% confidence level) for axions with mass up to 100 eV/c^{2}. This improves laboratory-based limits between about 1 eV/c^{2} and 100 eV/c^{2}.

Inhibition of Immunosuppressive Tumors by Polymer-Assisted Inductions of Immunogenic Cell Death and Multivalent PD-L1 Crosslinking.

Checkpoint blockade immunotherapies harness the host's own immune system to fight cancer, but only work against tumors infiltrated by swarms of pre-existing T cells. Unfortunately, most cancers to date are immune-deserted. Here, we report a polymer-assisted combination of immunogenic chemotherapy and PD-L1 degradation for efficacious treatment in originally non-immunogenic cancer. "Priming" tumors with backbone-degradable polymer-epirubicin conjugates elicits immunogenic cell death and fosters tumor-specific CD8+ T cell response. Sequential treatment with a multivalent polymer-peptide antagonist to PD-L1 overcomes adaptive PD-L1 enrichment following chemotherapy, biases the recycling of PD-L1 to lysosome degradation via surface receptor crosslinking, and produces prolonged elimination of PD-L1 rather than the transient blocking afforded by standard anti-PD-L1 antibodies. Together, these findings established the polymer-facilitated tumor targeting of immunogenic drugs and surface crosslinking of PD-L1 as a potential new therapeutic strategy to propagate a long-term antitumor immunity, which might broaden the application of immunotherapy to immunosuppressive cancers.

Early Signal of Emerging Nuclear Collectivity in Neutron-Rich

Radioactive ^{129}Sb, which can be treated as a proton plus semimagic ^{128}Sn core within the particle-core coupling scheme, was studied by Coulomb excitation. Reduced electric quadrupole transition probabilities, B(E2), for the 2^{+}⊗πg_{7/2} multiplet members and candidate πd_{5/2} state were measured. The results indicate that the total electric quadrupole strength of ^{129}Sb is a factor of 1.39(11) larger than the ^{128}Sn core, which is in stark contrast to the expectations of the empirically successful particle-core coupling scheme. Shell-model calculations performed with two different sets of nucleon-nucleon interactions suggest that this enhanced collectivity is due to constructive quadrupole coherence in the wave functions stemming from the proton-neutron residual interactions, where adding one nucleon to a core near a double-shell closure can have a pronounced effect. The enhanced electric quadrupole strength is an early signal of the emerging nuclear collectivity that becomes dominant away from the shell closure.

Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine.

Drug-free macromolecular therapeutics (DFMT) is a new paradigm for the treatment of B cell malignancies. Apoptosis is initiated by the biorecognition of complementary oligonucleotide motifs at the cell surface resulting in crosslinking of CD20 receptors. DMFT is composed from two nanoconjugates: 1) bispecific engager, Fab'-MORF1 (anti-CD20 Fab' fragment conjugated with morpholino oligonucleotide), and 2) a crosslinking (effector) component P-(MORF2)X (N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer grafted with multiple copies of complementary morpholino oligonucleotide). We evaluated this concept in 44 samples isolated from patients diagnosed with various subtypes of B cell malignancies. Apoptosis was observed in 65.9% of the samples tested. Pretreatment of cells with gemcitabine (GEM) or polymer-gemcitabine conjugate (2P-GEM) enhanced CD20 expression levels thus increasing apoptosis induced by DFMT. These positive results demonstrated that DFMT has remarkable therapeutic potential in various subtypes of B cell malignancies.

First Limit on the Direct Detection of Lightly Ionizing Particles for Electric Charge as Low as e/1000 with the Majorana Demonstrator.

The Majorana Demonstrator is an ultralow-background experiment searching for neutrinoless double-beta decay in ^{76}Ge. The heavily shielded array of germanium detectors, placed nearly a mile underground at the Sanford Underground Research Facility in Lead, South Dakota, also allows searches for new exotic physics. Free, relativistic, lightly ionizing particles with an electrical charge less than e are forbidden by the standard model but predicted by some of its extensions. If such particles exist, they might be detected in the Majorana Demonstrator by searching for multiple-detector events with individual-detector energy depositions down to 1 keV. This search is background-free, and no candidate events have been found in 285 days of data taking. New direct-detection limits are set for the flux of lightly ionizing particles for charges as low as e/1000.

Perceived stress and well-being in UK and Australian dental hygiene and dental therapy students.

INTRODUCTION: This study aimed to explore United Kingdom (UK) and Australian (Aus) dental hygiene and dental therapy students' (DHDTS) perception of stress and well-being during their undergraduate education. Upon qualification, DHDTS in the UK register as dental therapists (DT), and in Australia, they register as Oral Health Therapists (OHT). MATERIALS AND METHODS: A questionnaire was distributed to years 1, 2 and 3 DHDTS at the University of Portsmouth Dental Academy (UPDA) in the UK and La Trobe Rural Health School in Australia. The questionnaire consisted of 5 well-used measurement instruments which included the following: Dental Environment Stress questionnaire (DES); Depression Anxiety Stress Scales (DASS-21); Scales of Psychological Well-Being (SPWB); Valuing Questionnaire (VQ); and the Adult Hope Scale (AHS) to collect data on students' perception of levels of stress and well-being. RESULTS: A response rate of 58% (UK) and 55% (Australia) was achieved. Clinical factors and academic work were perceived as stressful for DHDTS in both the UK and Australia. The Australian DHDTS-perceived stress in the educational environment was significantly higher (P < .002) than the UK DHDTS. The majority of respondents reported levels of depression, anxiety and stress to be within the normal-to-moderate range. All students reported high levels of positive well-being, with no significant differences between the 2 groups. CONCLUSIONS: DHDTS in the UK and Australia identified sources of stress within their undergraduate education, but also perceived themselves as positively functioning individuals.

Electromagnetic Moments of Radioactive

Radioactive ^{136}Te has two valence protons and two valence neutrons outside of the ^{132}Sn double shell closure, providing a simple laboratory for exploring the emergence of collectivity and nucleon-nucleon interactions. Coulomb excitation of ^{136}Te on a titanium target was utilized to determine an extensive set of electromagnetic moments for the three lowest-lying states, including B(E2;0_{1}^{+}→2_{1}^{+}), Q(2_{1}^{+}), and g(2_{1}^{+}). The results indicate that the first-excited state, 2_{1}^{+}, composed of the simple 2p⊕2n system, is prolate deformed, and its wave function is dominated by excited valence neutron configurations, but not to the extent previously suggested. It is demonstrated that extreme sensitivity of g(2_{1}^{+}) to the proton and neutron contributions to the wave function provides unique insight into the nature of emerging collectivity, and g(2_{1}^{+}) was used to differentiate among several state-of-the-art theoretical calculations. Our results are best described by the most recent shell model calculations.

New Limits on Bosonic Dark Matter, Solar Axions, Pauli Exclusion Principle Violation, and Electron Decay from the Majorana Demonstrator.

We present new limits on exotic keV-scale physics based on 478 kg d of Majorana Demonstrator commissioning data. Constraints at the 90% confidence level are derived on bosonic dark matter (DM) and solar axion couplings, Pauli exclusion principle violating (PEPV) decay, and electron decay using monoenergetic peak signal limits above our background. Our most stringent DM constraints are set for 11.8 keV mass particles, limiting g_{Ae}<4.5×10^{-13} for pseudoscalars and (α^{'}/α)<9.7×10^{-28} for vectors. We also report a 14.4 keV solar axion coupling limit of g_{AN}^{eff}×g_{Ae}<3.8×10^{-17}, a 1/2ß^{2}<8.5×10^{-48} limit on the strength of PEPV electron transitions, and a lower limit on the electron lifetime of τ_{e}>1.2×10^{24} yr for e^{-}→ invisible.

Attitudes of the first cohort of student groups trained together at the University of Portsmouth Dental Academy towards dental interprofessional education.

OBJECTIVE: This study explored, and compared, the attitudes of student groups trained at the University of Portsmouth Dental Academy (UPDA) in 2010/2011 towards dental interprofessional education (IPE). METHODS: The study population consisted of fifth-year student dentists (n = 80) from King's College London Dental Institute, second- and third-year dental hygiene and therapy (n = 38) and first-year dental nursing (n = 14) students from UPDA. A 19-item, validated and dentally modified questionnaire, 'Readiness for Inter-Professional Learning Scale (RIPLS)', was administered. RIPLS contains three subscales: teamwork and collaboration, professional identity and roles and responsibilities. Mean (x¯) and standard deviation (SD) of the scores were calculated, following reversal of negative items. All the analyses were carried out using SPSS version 20 and STATA version 11. RESULTS: An overall response rate of 71% (n = 94) was achieved. In reference to teamwork and collaboration, all groups strongly indicated that IPE can contribute to learning teamwork skills (x¯ = 24.98, SD = 3.5) and improving relationships with team members (x¯ = 12.93, SD = 1.63); however, the scores did not differ between the groups (P = 0.09 and P = 0.16, respectively). Concerning professional identity, student dentists had significantly higher preference for a discipline-based approach (P = 0.002); were more likely to agree that 'it is not necessary for undergraduate dental and dental care professional students to learn together' (P = 0.01); and perceived that 'clinical problem-solving skills can only be learnt effectively with other students from their own discipline' (P = 0.02) than dental hygiene and therapy students. In relation to roles and responsibilities, participants demonstrated a strong sense of their own professional role. Student dentists reported that they had 'to gain more knowledge and skills' than dental hygiene and therapy (P = 0.01) and dental nursing (P = 0.01) students. Dental hygiene and therapy students were less likely than student dentists to agree that 'the role of dental nurses and hygienists was to mainly provide support for dentists' (P = 0.001). CONCLUSION: The findings suggest that IPE was perceived as beneficial in relation to teamwork; however, the study raises issues regarding professional identity and roles. Educators should consider differing perceptions of professional roles and identities when planning and delivering interprofessional programmes.

Outreach clinical dental education: the Portsmouth experience - a 4-year follow-up study.

BACKGROUND: The Portsmouth Dental Academy (UPDA) was opened in September 2010 and was a development from the highly successful School of Professionals Complementary to Dentistry (2004-2010). The aim of the Academy was to provide integrated team education for all dental professionals in a primary care setting. The dental students are on outreach from King's College London, and the dental care professional students are registered at the University of Portsmouth. OBJECTIVES: To evaluate the dental students response to the residential outreach educational experience at the UPDA. METHODS: A 49-item questionnaire divided into nine domains that provided both qualitative data and quantitative data were administered at the end of the longitudinal 10-week placement, to four successive cohorts of students in 2010-2014. RESULTS: A 95% return rate was achieved. Students valued highly the quality of the clinical teaching. Through their experience, they felt they understood fully the role of the dentist in care planning in primary care and felt well prepared for dental foundation training. This educational success is unpinned with successful maintenance factors including a well-organised induction period and giving the students a sense of belongingness, empowerment and autonomy for their personal development as new graduates. CONCLUSION: Within the limitations of the questionnaire study over the 4-year period, the students were very positive about all the aspects of this residential outreach education at the UPDA but particularly valued the immersion in clinical dentistry and the bridging from dental school to their dental foundation training.

Rational design of "heat seeking" drug loaded polypeptide nanoparticles that thermally target solid tumors.

This paper demonstrates the first example of targeting a solid tumor that is externally heated to 42 °C by "heat seeking" drug-loaded polypeptide nanoparticles. These nanoparticles consist of a thermally responsive elastin-like polypeptide (ELP) conjugated to multiple copies of a hydrophobic cancer drug. To rationally design drug-loaded nanoparticles that exhibit thermal responsiveness in the narrow temperature range between 37 and 42 °C, an analytical model was developed that relates ELP composition and chain length to the nanoparticle phase transition temperature. Suitable candidates were designed based on the predictions of the model and tested in vivo by intravital confocal fluorescence microscopy of solid tumors, which revealed that the nanoparticles aggregate in the vasculature of tumors heated to 42 °C and that the aggregation is reversible as the temperature reverts to 37 °C. Biodistribution studies showed that the most effective strategy to target the nanoparticles to tumors is to thermally cycle the tumors between 37 and 42 °C. These nanoparticles set the stage for the targeted delivery of a range of cancer chemotherapeutics by externally applied mild hyperthermia of solid tumors.

Double-magic nature of 132Sn and 208Pb through lifetime and cross-section measurements.

Single-neutron states in (133)Sn and (209)Pb, which are analogous to single-electron states outside of closed atomic shells in alkali metals, were populated by the ((9)Be, (8)Be) one-neutron transfer reaction in inverse kinematics using particle-γ coincidence spectroscopy. In addition, the s(1/2) single-neutron hole-state candidate in (131)Sn was populated by ((9)Be, (10)Be). Doubly closed-shell (132)Sn (radioactive) and (208)Pb (stable) beams were used at sub-Coulomb barrier energies of 3 MeV per nucleon. Level energies, γ-ray transitions, absolute cross sections, spectroscopic factors, asymptotic normalization coefficients, and excited-state lifetimes are reported and compared with shell-model expectations. The results include a new transition and precise level energy for the 3p(1/2) candidate in (133)Sn, new absolute cross sections for the 1h(9/2) candidate in (133)Sn and 3s(1/2) candidate in (131)Sn, and new lifetimes for excited states in (133)Sn and (209)Pb. This is the first report on excited-state lifetimes of (133)Sn, which allow for a unique test of the nuclear shell model and (132)Sn double-shell closure.

A unified model for de novo design of elastin-like polypeptides with tunable inverse transition temperatures.

Elastin-like polypeptides (ELPs) are stimulus-responsive peptide polymers that exhibit inverse temperature phase transition behavior, causing an ELP to aggregate above its inverse transition temperature (T(t)). Although this property has been exploited in a variety of biotechnological applications, de novo design of ELPs that display a specific T(t) is not trivial because the T(t) of an ELP is a complex function of several variables, including its sequence, chain length, polypeptide concentration, and the type and concentration of cosolutes in solution. This paper provides a quantitative model that predicts the T(t) of a family of ELPs (Val-Pro-Gly-Xaa-Gly, where Xaa = Ala and/or Val) from their composition, chain length, and concentration in phosphate buffered saline. This model will enable de novo prediction of the amino acid sequence and chain length of ELPs that will display a predetermined T(t) in physiological buffer within a specified concentration regime, thereby greatly facilitating the design of new ELPs for applications in medicine and biotechnology.

The relationship between access to and use of dental services following expansion of a primary care service to embrace dental team training.

OBJECTIVES: To investigate changes in the patient population and treatment case-mix within an expanded primary care dental training facility in Southern England. STUDY DESIGN: Cross-sectional analysis of patient management system data. METHOD: Electronic data for patients with a closed/completed treatment plan in the 12-month period prior to, and following, dental service expansion were extracted for analysis (n = 4343). Descriptive analysis involved age, sex, payment status, deprivation status and treatment activity. Logistic regression was used to model the likelihood of treatment involving laboratory constructed devices (crowns, bridges, dentures), in relation to demography and deprivation in each time period. RESULTS: The volume of patients using the service increased by 48.3% (1749 cf 2594). The average age increased from 31.97 (95%CI: 30.8, 32.5) to 36.4 years (95%CI: 35.6, 37.1); greatest increase was in the over 75 years age-group (96%). The patient base became less deprived: patients exempt from payment reduced from 43.2% (n = 755) to 28.6% (n = 741) (P = 0.001) and the mean population deprivation score (IMD) reduced from 24.5 (95%CI: 23.8, 25.2) to 22.3 (95%CI: 21.7, 22.8). The volume and proportion of care involving laboratory constructed devices increased from 8.3% (n = 145) to 15.8% (n = 411) whilst assessments without interventive care decreased (34.5%-26.3%). On a logistic regression, the odds of having treatment involving laboratory constructed devices, increased with increasing age in both time periods 7% (95% CI: 1.06-1.08) and 6% (95% CI: 1.05-1.07) respectively. Furthermore, the odds increased by 38% OR: 1.38 (95% CI: 1.01-1.89) in period 2, for white patients. After adjusting for these effects, the odds of having care that involved laboratory constructed devices were less in period 2 than period 1 (100% cf 43%) for those who were technically exempt from payment (OR = 2.0; 95% CI 1.34 to 2.90 cf, OR = 1.43; 95% CI 1.13-1.81). CONCLUSION: The patient population altered in relation to age and socio-economic status. The expanded service had greater uptake by older people while users were less likely to be deprived. The expanded service, free at the point of delivery, attracted a higher proportion of patients who would normally have to pay health service charges. The service also showed an increase in treatment case-mix that involved laboratory constructed dental devices.

BRCA2 germline mutations in male breast cancer cases and breast cancer families.

The breast cancer susceptibility gene, BRCA2 on chromosome 13q12-13, was recently isolated. Mutations in BRCA2 are thought to account for as much as 35% of all inherited breast cancer as wall as a proportion of inherited ovarian cancer. Many BRCA2-linked families also contain cases of male breast cancer. We have analysed germline DNA from 50 males with breast cancer (unselected for family history) and 26 individuals from site-specific female breast and breast-ovarian cancer families for mutations in BRCA2. All 17 breast-ovarian cancer families have been screened for BRCA1 coding region mutations and none were detected. Conformation-sensitive gel electrophoresis (CSGE) analysis of PCR-amplified DNA followed by direct sequencing was used to detect sequence variants. Three of eleven individuals carry the same mutation, all are of Ashkenazi Jewish descent, supporting the observation by Neuhausen et al. in this issue that there is a common mutation in this population. Eleven truncating mutations and nine polymorphisms were identified -- all were coding region variants. No loss-of-transcript mutations were identified in the sixteen samples for which this analysis was possible. Seven of the nine disease-associated mutations were detected in the 50 men with breast cancers; for thus in our series, BRCA2 mutations account for 14% of male breast cancer, all but one of which had a family history of male and/or female breast cancer.