Self-compensation in manganese-doped ferromagnetic semiconductors

We present a theory of interstitial Mn in Mn-doped ferromagnetic semiconductors. Using density-functional theory, we show that under the non-equilibrium conditions of growth, interstitial Mn is easily formed near the surface by a simple low-energy adsorption pathway. In GaAs, isolated interstitial Mn is an electron donor, each compensating two substitutional Mn acceptors. Within an impurity-band model, partial compensation promotes ferromagnetic order below the metal-insulator transition, with the highest Curie temperature occurring for 0.5 holes per substitutional Mn.Comment: 4 pages, 3 figures, to appear in Phys. Rev. Let

Predictors of Gains During Inpatient Rehabilitation in Patients with Stroke- A Review.

Stroke remains a major cause of disability. The cost of stroke rehabilitation is substantial. Understanding the factors that predict response to inpatient stroke rehabilitation may be useful, for example, to best individualize the content of therapy, or to maximize the efficiency with which resources are directed. This review reviewed the literature and found that numerous variables were associated with outcome after inpatient stroke rehabilitation. The strongest evidence exists for factors such as age, stroke subtype, nutritional status, psychosocial factors such as living with family prior to stroke or presence of a caregiver. Functional status on admission, urinary incontinence, post-stroke infection, and aphasia each can also impact prognosis. Strengths and weaknesses of cited studies are considered in an attempt to inform design of future studies examining the factors that predict response to inpatient rehabilitation after stroke

Rapid activation of dormant presynaptic terminals by phorbol esters

Presynaptic stimulation stochastically recruits transmission according to the release probability (P(r)) of synapses. The majority of central synapses have relatively low P(r), which includes synapses that are completely quiescent presynaptically. The presence of presynaptically dormant versus active terminals presumably increases synaptic malleability when conditions demand synaptic strengthening or weakening, perhaps by triggering second messenger signals. However, whether modulator-mediated potentiation involves recruitment of transmission from dormant terminals remains unclear. Here, by combining electrophysiological and fluorescence imaging approaches, we uncovered rapid presynaptic awakening by select synaptic modulators. A phorbol ester phorbol 12,13-dibutyrate (PDBu, a diacylglycerol analog), but not forskolin (an adenylyl cyclase activator) or elevated extracellular calcium, recruited neurotransmission from presynaptically dormant synapses. This effect was not dependent on protein kinase C activation. After PDBu-induced awakening, these previously dormant terminals had a synaptic P(r) spectrum similar to basally active synapses naive to PDBu treatment. Dormant terminals did not seem to have properties of nascent or immature synapses, judged by NR2B N-methyl-D-aspartate receptor (NMDAR) receptor subunit contribution after PDBu-stimulated awakening. Strikingly, synapses rendered inactive by prolonged depolarization, unlike basally dormant synapses, were not awakened by PDBu. These results suggest that the initial release competence of synapses can dictate the acute response to second messenger modulation, and the results suggest multiple pathways to presynaptic dormancy and awakening

Identification of RPS14 as a 5q- syndrome gene by RNA interference screen

Somatic chromosomal deletions in cancer are thought to indicate the location of tumor suppressor genes, whereby complete loss of gene function occurs through biallelic deletion, point mutation, or epigenetic silencing, thus fulfilling Knudson's two-hit hypothesis.1 In many recurrent deletions, however, such biallelic inactivation has not been found. One prominent example is the 5q- syndrome, a subtype of myelodysplastic syndrome (MDS) characterized by a defect in erythroid differentiation.2 Here, we describe an RNA interference (RNAi)-based approach to discovery of the 5q- disease gene. We find that partial loss of function of the ribosomal protein RPS14 phenocopies the disease in normal hematopoietic progenitor cells, and moreover that forced expression of RPS14 rescues the disease phenotype in patient-derived bone marrow cells. In addition, we identified a block in the processing of pre-rRNA in RPS14 deficient cells that is highly analogous to the functional defect in Diamond Blackfan Anemia, linking the molecular pathophysiology of the 5q- syndrome to a congenital bone marrow failure syndrome. These results indicate that the 5q- syndrome is caused by a defect in ribosomal protein function, and suggests that RNAi screening is an effective strategy for identifying causal haploinsufficiency disease genes

Cetuximab and anemia prevention in head and neck cancer patients undergoing radiotherapy

BACKGROUND: Epidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels intensifies RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, has been associated with lower rates of anemia for locally advanced head and neck squamous cell carcinoma (HNSCC). We hypothesized that concomitant cetuximab could prevent RT-induced anemia. METHODS: We queried our institutional head and neck cancers database for non-metastatic HNSCC cases that received RT with concomitant cetuximab or RT-only between 2006 and 2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. We only included patients who had at least one complete blood count in the 4 months preceding and after RT. We compared the prevalence of anemia (defined as hemoglobin (Hb) below 12 g/dL in females and 13 g/dL in males) and mean Hb levels at baseline and after RT. Improvement of anemia/Hb (resolution of baseline anemia and/or an increase of baseline Hb ≥1 g/dL after RT), and overall survival (OS) in relation to anemia/Hb dynamics were also compared. RESULTS: A total of 171 patients were identified equally distributed between cetuximab-plus-RT and RT-only groups. The cetuximab-plus-RT group had more locally-advanced stage, oropharyngeal and high grade tumors (p \u3c 0.001 for all). Baseline anemia/Hb were similar, however anemia after RT conclusion was higher in the cetuximab-plus-RT vs RT-only (63.5% vs. 44.2%; p = 0.017), with a mean Hb of 11.98 g/dL vs. 12.9 g/dL; p = 0.003, for both respectively. This contributed to significantly worse anemia/Hb improvement for cetuximab-plus-RT (18.8% vs. 37.2%; p = 0.007). This effect was maintained after adjusting for other factors in multivariate analysis. The prevalence of iron, vitamin-B12 and folate deficiencies; and chronic kidney disease, was non-different. Baseline anemia was associated with worse OS (p = 0.0052) for the whole study cohort. Nevertheless, improvement of anemia/Hb was only marginally associated with better OS (p = 0.068). CONCLUSIONS: In contrast to previous studies, cetuximab was not associated with lower rates of anemia after RT for nonmetastatic HNSCC patients compared to RT-alone. Dedicated prospective studies are needed to elucidate the effect of cetuximab on RT-induced anemia

Semiclassical Theory of Coulomb Blockade Peak Heights in Chaotic Quantum Dots

We develop a semiclassical theory of Coulomb blockade peak heights in chaotic quantum dots. Using Berry's conjecture, we calculate the peak height distributions and the correlation functions. We demonstrate that the corrections to the corresponding results of the standard statistical theory are non-universal and can be expressed in terms of the classical periodic orbits of the dot that are well coupled to the leads. The main effect is an oscillatory dependence of the peak heights on any parameter which is varied; it is substantial for both symmetric and asymmetric lead placement. Surprisingly, these dynamical effects do not influence the full distribution of peak heights, but are clearly seen in the correlation function or power spectrum. For non-zero temperature, the correlation function obtained theoretically is in good agreement with that measured experimentally.Comment: 5 color eps figure