ABSTRACr When the magnetic susceptibility of frozen aqueous solutions of human oxyhemoglobin was measured in the range between 25 and 250 K, it showed a temperatur ependent behavior typical of a thermal equilibrium between a ground singlet state and an excited triplet state for two electrons per heme, the energy separation being 12JI = 146 cm-1. By contrast, within the same temperature range, carboxyhemoglobin was found to be diamagnetic, as already reported.Since the first magnetic studies by Pauling and Coryell (1), the electronic state of iron and oxygen in oxyhemoglobin (HbO2) has been the subject of continuous debate. Five different models for 02 binding in HbO2 have been proposed on the basis of various theoretical interpretations of the available experimental evidence (2)(3)(4)(5)(6).The presence of unpaired electrons in the iron-oxygen bond has been inferred from x-ray fluorescence spectra (7), from spectroscopy data and analogy with cobalt complexes (8, 9), and from M6ssbauer (10) and Raman (11) Optical spectra of the samples were recorded by a Beckman DK-2A spectrophotometer before and after the susceptibility measurement. The concentration of methemoglobin (MetHb) in the samples was estimated to be less than 3% in all cases. To avoid any possible interferences from MetHb, we added KCN to stripped HbO2 to stabilize the MetHb in the low-spin form (15) at any temperature. Measurements were performed on several different preparations of Hb. The temperature-dependent susceptibility was measured at least twice on each sample. RESULTS AND DISCUSSIONTo emphasize the small differences between HbO2 and HbCO samples, all the data were normalized to give the same extrapolation for infinite temperature, which was set as the value extracted from the data of Havemann (16) for HbCO. Typical results for stripped HbO2 and HbCO equilibrated with air, 02 at 1 atm, and CO at 1 atm, are presented in Fig. 1.There is a striking difference in behavior. The stripped HbCO showed a weak Curie law paramagnetic contribution which is quantitatively accounted for by the presence of 0.85% MetHb in the low-spin state.Native HbCO gave similar results, with an even smaller paramagnetic contribution. We conclude that both native and stripped HbCO are diamagnetic. We also conclude that (i) no sample density effects interfered with the volume susceptibility measurements within our resolution and (ii) MetHb, if any, must stay in the same low-spin state in the whole temperature range scanned and strictly obey a simple Curie law.The temperature dependence of the magnetic susceptibility of the frozen solutions of stripped HbO2 was strikingly different from that of HbCO.To fit the data we needed a composite temperature-dependent behavior that allows for the presence of a Curie law paramagnetic component plus a paramagnetic contribution nonlinear in inverse temperature, representing a thermal equilibrium between a ground singlet state and an excited triplet state. The Curie law paramagnetic contribution is easily assigned to the paramagnetis...

The magnetic susceptibility and the density of human oxy-(HbO2) and carbonmonoxyhemoglobin (HbCO) solutions of various concentrations have been measured at room temperature, with pure water used as a calibrant. Solutions of unstripped and stripped HbO2 at pH 7.2 in unbuffered water solvent were always found to be less diamagnetic than pure water, whereas solutions of HbCO in identical conditions were always found to be more diamagnetic than pure water. After correcting for concentration-dependent density changes and assuming the HbCO samples to be fully diamagnetic, the paramagnetic reduction of the diamagnetic susceptibility of HbO2 corresponds to a molar susceptibility per heme (XMheme) of 2460 + 600 X 10-6 cgs/mol. Our finding that frozen solutions of human HbO2 show significant deviations from diamagnetism (1) has revived the debate on the electronic state of oxyheme (2)(3)(4)(5)(6). We know of no other direct measurement of the susceptibility that has appeared since then; recent theoretical calculations give a diamagnetic ground state, in accord with our results (1), at the lowest temperatures but suggest (3, 7-9) various different energies for a low-lying triplet state, ranging up to about 8000 cm-1. Except for ref. 7, all are inconsistent with our results which suggest a singlet-triplet separation of only about 150 cm-1 but in accord with the classical work of Pauling and Coryell (10) which described HbO2 as diamagnetic. Our lowtemperature data are not directly relevant to a discussion of the room-temperature magnetic properties of HbO2 because in some hemoglobin derivatives the magnetic state of the iron ion may be irreversibly or reversibly altered upon freezing the solution. We have compared the volume susceptibility of solutions of stripped and unstripped human HbO2 at room temperature at pH 7.2, in the concentration range 5 to 25 mM in heme, to that of similar solutions of the carboxy derivative and of samples of pure water by using our SQUID susceptometer (11) as before (1). For a quantitative analysis, precise knowledge of the density of the solutions was essential and we have measured this as a function of protein concentration. MATERIALS AND METHODSHb solutions were prepared according to Benesch et al. (12) from blood freshly drawn from one of us (B.P.). The end products were unbuffered solutions of HbO2 about 9 mM in heme at pH close to 7 equilibrated with air. Overnight dialysis in the cold provided solutions of higher concentration, when needed, and, as a final step, KCN was added to a molar concentration of 15% of that of the heme to stabilize any metHb present in the low-spin form (13). At this stage, each sample was divided into two parts. One half was stored at 40 until used. The other half was gently shaken and flu-shed repeatedly in the cold with high-purity wet CO in a home-made tonometer for 1.5 hr. Optical spectra of the samples were taken after dialysis and after magnetic measurements to determine the heme concentration. A detailed analysis of the samples was also perform...

Apocrine carcinoma of the skin is a rare tumor. Wide surgical excision with complete removal of the neoplasm is the standard therapy and this appears to offer the best chance of cure. Radiotherapy may be used in case of local relapse or regional lymph node involvement. Systemic chemotherapy has not proved to be effective in the treatment of this tumor. We report on a 46-year-old woman with a recurrent apocrine carcinoma of the scalp that had previously been treated with surgery, radiotherapy and chemotherapy (Al-Saraff schedule). The patient was responsive to a second-line systemic chemotherapy regimen consisting of a weekly combination of methotrexate and bleomycin, and achieved long-term progression-free survival.

Galactic cosmic-ray (GCR) energy spectra observed in the inner heliosphere are modulated by the solar activity, the solar polarity and structures of solar and interplanetary origin. A high counting rate particle detector (PD) aboard LISA Pathfinder, meant for subsystems diagnostics, was devoted to the measurement of GCR and solar energetic particle integral fluxes above 70 MeV n −1 up to 6500 counts s −1 . PD data were gathered with a sampling time of 15 s. Characteristics and energy dependence of GCR flux recurrent depressions and of a Forbush decrease dated 2016 August 2 are reported here. The capability of interplanetary missions, carrying PDs for instrument performance purposes, in monitoring the passage of interplanetary coronal mass ejections is also discussed.

We use 47 gravitational wave sources from the Third LIGO–Virgo–Kamioka Gravitational Wave Detector Gravitational Wave Transient Catalog (GWTC–3) to estimate the Hubble parameter H(z), including its current value, the Hubble constant H 0. Each gravitational wave (GW) signal provides the luminosity distance to the source, and we estimate the corresponding redshift using two methods: the redshifted masses and a galaxy catalog. Using the binary black hole (BBH) redshifted masses, we simultaneously infer the source mass distribution and H(z). The source mass distribution displays a peak around 34 M ⊙, followed by a drop-off. Assuming this mass scale does not evolve with the redshift results in a H(z) measurement, yielding H 0 = 68 − 8 + 12 km s − 1 Mpc − 1 (68% credible interval) when combined with the H 0 measurement from GW170817 and its electromagnetic counterpart. This represents an improvement of 17% with respect to the H 0 estimate from GWTC–1. The second method associates each GW event with its probable host galaxy in the catalog GLADE+, statistically marginalizing over the redshifts of each event’s potential hosts. Assuming a fixed BBH population, we estimate a value of H 0 = 68 − 6 + 8 km s − 1 Mpc − 1 with the galaxy catalog method, an improvement of 42% with respect to our GWTC–1 result and 20% with respect to recent H 0 studies using GWTC–2 events. However, we show that this result is strongly impacted by assumptions about the BBH source mass distribution; the only event which is not strongly impacted by such assumptions (and is thus informative about H 0) is the well-localized event GW190814.