Recent Development: Varriale v. State: The State May Store and Use a Voluntarily Provided DNA Sample and Resultant Profile For Any Future Criminal Investigations, Unless the Suspect Provides an Express Limitation

The Court of Appeals of Maryland held that when a suspect does not expressly limit consent to DNA testing, the Fourth Amendment does not prevent the State from storing and using his voluntarily provided DNA in later, unrelated criminal investigations

Recent Development: Varriale v. State: The State May Store and Use a Voluntarily Provided DNA Sample and Resultant Profile For Any Future Criminal Investigations, Unless the Suspect Provides an Express Limitation

The Court of Appeals of Maryland held that when a suspect does not expressly limit consent to DNA testing, the Fourth Amendment does not prevent the State from storing and using his voluntarily provided DNA in later, unrelated criminal investigations

A Gold-Catalyzed Entry into the Sesquisabinene and Sesquithujene Families of Terpenoids and Formal Total Syntheses of Cedrene and Cedrol

A concise entry into the bicyclic cyclopropyl ketone derivatives 5 and 6 by way of a gold-catalyzed Ohloff–Rautenstrauch-type enyne cycloisomerization is described. The required substrates were prepared by an asymmetric addition of the branched allylzinc reagent 21 to the alkynyl aldehyde 17 mediated by the deprotonated bisoxazoline (BOX) ligand 22. Compounds 5 and 6 were then converted into a host of different members of the sesquisabina- and sesquithuja families of terpenoids, inter alia with the aid of iron-catalyzed cross-coupling reactions. As the relative and absolute configuration of 5 and 6 could be unambiguously established, the synthetic samples allowed the previously unknown stereostructures of various such terpenoids to be unraveled, including cis-sesquisabinene hydrate (33), 7-epi-sesquithujene (36), sesquisabinene B (37) and epoxy-sesquithujene (45). Moreover, the preparation of 6 also constitutes a formal total synthesis of cedrene (11) and cedrol (12)

Facile formation of iodocyclobutenes by a ruthenium-catalyzed enyne cycloisomerization

Enynes bearing an iodide (bromide) at their alkyne terminus react with catalytic amounts of [Cp*Ru(MeCN)3]PF6 in DMF to give strained iodo(bromo)cyclobutene derivatives in good to excellent yields

The role of tumor-infiltrating MDSC subsets in tumor progression

Several mechanisms have been proposed for profound immune impairments that accompany tumor development. Alteration in myelopoiesis that occur during tumor growth leads to the accumulation and recruitment of immunosuppressive cells, known as myeloid-suppressor cells (MDSCs). MDSCs have been characterized in cancer patients and tumor bearing mice based on their ability to suppress T cell responses. During tumor progression MDSCs accumulate in bone marrow, blood, peripheral lymphoid organs and in the tumor tissue. They represent a heterogeneous population of myeloid cells at different stages of differentiation. In mice these cells are characterized by the co-expression of the surface markers Gr-1 and CD11b. Within this population, two distinct MDSC subpopulations with clear morphological differences have been identified, comprising mononuclear cells (MO-MDSCs), which express Ly6C and the macrophage marker F4/80, and polymorphonuclear cells (PMN-MDSCs), which express Ly6G and do not display F4/80 surface expression. The aim of this thesis was to determine the distribution of tumor-infiltrating and blood MDSC subsets as well as the molecular signature and function of genes differently regulated in MDSC subpopulations. We demonstrated that after subcutaneous injection of RMA-S tumor cells, both MDSC subsets accumulated in the tumor tissue. Gene expression profiling of blood and tumor-infiltrating MDSCs using whole genome microarrays revealed profound changes in the transcription profile between MDSC subsets in blood and tumor. Tumor-infiltrated MO-MDSCs displayed increased expression of genes involved in suppression, inflammatory responses and chemotaxis compared to blood MDSCs. We confirmed that differentially regulated genes at mRNA level were also differently expressed at protein levels and might play a significant role in MDSC function. In addition, tumor-infiltrating MDSCs showed an increased surface expression of TLR-4, CD14, and Dectin-2, suggesting a pro-inflammatory phenotype of these subsets in the tumor tissue. Stimulation of the CD14/TLR-4 complex with LPS resulted in an upregulation of the NKG2D ligand Rae-1, which might be involved in natural killer cell activation. Compared to blood MDSCs, the activity of suppressive factors such as arginase-1 and iNOS was increased in tumor-infiltrating MO-MDSCs. In addition, we observed that only tumor-infiltrating MO-MDSCs expressed high amount of several chemokines including three ligands of the chemokine receptor CCR5: CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES). Intra-tumoral injection of these recombinant chemokines resulted in an increased accumulation of regulatory T cells and a lower CD8+/Treg ratio in the tumor tissue correlated with accelerated tumor growth and shortened survival of tumor-bearing mice. On the contrary, CCR5 deficient mice injected with RMA-S tumor cells showed reduced tumor growth and prolonged survival associated with high numbers of CD4+ and CD8+ T cells and an increased CD8+/Treg ratio detected in the tumor. In summary, we demonstrated that tumor-infiltrating MO-MDSCs exerted key features to promote tumor progression. Increased expression of suppressive factors by MO-MDSC in the tumor tissue might directly downmodulate T cell responses, whereas chemokine secretion might induce the accumulation of tumor-infiltrating regulatory T cells, resulting in additive immune suppression. Those findings defined a new regulatory role of MDSCs in recruiting Tregs, which might be clinically relevant in developing novel immunotherapeutic strategies for cancer patients

On the modeling of amplitude-sensitive electron spin resonance (ESR) detection using voltage-controlled oscillator (VCO)-based ESR-on-a-chip detectors

In this paper, we present an in-depth analysis of a voltage-controlled oscillator (VCO)-based sensing method for electron spin resonance (ESR) spectroscopy, which greatly simplifies the experimental setup compared to conventional detection schemes. In contrast to our previous oscillator-based ESR detectors, where the ESR signal was encoded in the oscillation frequency, in the amplitude-sensitive method, the ESR signal is sensed as a change of the oscillation amplitude of the VCO. Therefore, using VCO architecture with a built-in amplitude demodulation scheme, the experimental setup reduces to a single permanent magnet in combination with a few inexpensive electronic components. We present a theoretical analysis of the achievable limit of detection, which uses perturbation-theory-based VCO modeling for the signal and applies a stochastic averaging approach to obtain a closed-form expression for the noise floor. Additionally, the paper also introduces a numerical model suitable for simulating oscillator-based ESR experiments in a conventional circuit simulator environment. This model can be used to optimize sensor performance early on in the design phase. Finally, all presented models are verified against measured results from a prototype VCO operating at 14 GHz inside a 0.5 T magnetic field

Bioverse: The Habitable Zone Inner Edge Discontinuity as an Imprint of Runaway Greenhouse Climates on Exoplanet Demographics

Long-term magma ocean phases on rocky exoplanets orbiting closer to their star than the runaway greenhouse threshold - the inner edge of the classical habitable zone - may offer insights into the physical and chemical processes that distinguish potentially habitable worlds from others. Thermal stratification of runaway planets is expected to significantly inflate their atmospheres, potentially providing observational access to the runaway greenhouse transition in the form of a "habitable zone inner edge discontinuity" in radius-density space. Here, we use Bioverse, a statistical framework combining contextual information from the overall planet population with a survey simulator, to assess the ability of ground- and space-based telescopes to test this hypothesis. We find that the demographic imprint of the runaway greenhouse transition is likely detectable with high-precision transit photometry for sample sizes $\gtrsim 100$ planets if at least ~10 % of those orbiting closer than the habitable zone inner edge harbor runaway climates. Our survey simulations suggest that in the near future, ESA's PLATO mission will be the most promising survey to probe the habitable zone inner edge discontinuity. We determine survey strategies that maximize the diagnostic power of the obtained data and identify as key mission design drivers: 1. A follow-up campaign of planetary mass measurements and 2. The fraction of low-mass stars in the target sample. Observational constraints on the runaway greenhouse transition will provide crucial insights into the distribution of atmospheric volatiles among rocky exoplanets, which may help to identify the nearest potentially habitable worlds.Comment: Accepted for publication in The Planetary Science Journal. For a video abstract, see https://youtu.be/acgKcdTTv9c. 29 pages, 12 figures, 1 table. All source code is available at https://github.com/matiscke/hz-inner-edge-discontinuit