Advanced-Stage Parkinson's Disease: From Identification to Characterization Using a Nationwide Database.

Background: As Parkinson's disease (PD) progresses, response to oral medications decreases and motor complications appear. Timely intervention has been demonstrated as effective in reducing symptoms. However, current instruments for the identification of these patients are often complicated and inadequate. It has been suggested that anti-PD intensified therapy (IT) can serve as a proxy for increased burden of disease. Objective: To explore whether IT aligns with events reflecting advanced PD (APD) burden. Methods: This was a retrospective analysis of PD beneficiaries in the second-largest healthcare provider in Israel. Patients with PD diagnosed between January 2000 and June 2018 and treated with levodopa (l-dopa) ≥5 times/day and/or ≥1000 mg l-dopa equivalent daily dose were defined as the IT cohort (n = 2037). Treated patients with PD not fulfilling this criterion were defined as the nonintensified therapy (NIT) cohort (n = 3402). Point prevalence and 5- and 10-year cumulative incidence of IT were assessed. Baseline demographic and comorbidities, 1-year healthcare resource use, health costs, and time to clinical events were assessed and compared between cohorts. Results: IT was associated with significantly (P < 0.05) higher healthcare resource use compared with NIT. In turn, IT patients incurred higher healthcare costs (P < 0.001) and were at greater risk for mortality, hospitalization, disability, and device-aided therapy use (P < 0.001, for all comparisons). Conclusions: Treatment intensity can serve as an objective and robust indicator of more APD. This readily extractable marker can be easily integrated into electronic medical record alerts to actively target more advanced patients and to guide risk-appropriate care.

Long-Term Persistence and Monotherapy with Device-Aided Therapies: A Retrospective Analysis of an Israeli Cohort of Patients with Advanced Parkinson's Disease.

INTRODUCTION: Patients with advanced Parkinson's disease (PD) may require device-aided therapies (DAT) for adequate symptom control. However, long-term, real-world efficacy and safety data are limited. This study aims to describe real-world, long-term treatment persistence for patients with PD treated with levodopa-carbidopa intestinal gel (LCIG). The study also aims to describe patient profiles, treatment discontinuation rates, co-medication patterns, monotherapy rates, and rates of healthcare visits and their associated costs for patients receiving all forms of DAT (deep brain stimulation [DBS], continuous subcutaneous apomorphine infusion [CSAI], or LCIG). METHODS: In this retrospective analysis of the Israeli Maccabi Healthcare Services database, adult patients with PD were analyzed in three cohorts, based on DAT (DBS, CSAI, or LCIG). The primary endpoint was LCIG treatment persistence 12 months after initiation. RESULTS: This analysis included 161 DAT-treated patients (LCIG, n = 62; DBS, n = 76; CSAI, n = 23). Among those who discontinued, the mean time to discontinuation was 86.4 months for LCIG and 42.4 months for CSAI (p = 0.046). Twelve months after initiation, 14.3% LCIG, 10.7% DBS, and 5.9% CSAI patients were not receiving any additional anti-parkinsonian therapy. At the last recorded visit, 28.6% LCIG, 13.3% DBS, and 5.9% CSAI patients received DAT as monotherapy. During the first 12 months after initiation, 45.2% LCIG, 65.2% CSAI, and 1.3% DBS patients had no reported hospitalization days. Annual healthcare visit costs decreased following LCIG initiation (US$9491 vs. $8146) and increased following DBS ($4113 vs. $7677) and CSAI ($6378 vs. $8277). CONCLUSION: DAT are well maintained in patients with advanced PD. These retrospective data suggest that patients receiving LCIG may have higher long-term persistence rates compared with patients receiving CSAI. A subgroup of patients was treated with DAT as monotherapy without additional oral anti-parkinsonian therapy, with LCIG showing the highest rates.

Byzantine-Early Islamic resource management detected through micro-geoarchaeological investigations of trash mounds (Negev, Israel).

Sustainable resource management is of central importance among agrarian societies in marginal drylands. In the Negev Desert, Israel, research on agropastoral resource management during Late Antiquity emphasizes intramural settlement contexts and landscape features. The importance of hinterland trash deposits as diachronic archives of resource use and disposal has been overlooked until recently. Without these data, assessments of community-scale responses to societal, economic, and environmental disruption and reconfiguration remain incomplete. In this study, micro-geoarchaeological investigations were conducted on trash mound features at the Byzantine-Early Islamic sites of Shivta, Elusa, and Nesanna to track spatiotemporal trends in the use and disposal of critical agropastoral resources. Refuse derived sediment deposits were characterized using stratigraphy, micro-remains (i.e., livestock dung spherulites, wood ash pseudomorphs, and plant phytoliths), and mineralogy by Fourier transform infrared spectroscopy. Our investigations detected a turning point in the management of herbivore livestock dung, a vital resource in the Negev. We propose that the scarcity of raw dung proxies in the studied deposits relates to the use of this resource as fuel and agricultural fertilizer. Refuse deposits contained dung ash, indicating the widespread use of dung as a sustainable fuel. Sharply contrasting this, raw dung was dumped and incinerated outside the village of Nessana. We discuss how this local shift in dung management corresponds with a growing emphasis on sedentised herding spurred by newly pressed taxation and declining market-oriented agriculture. Our work is among the first to deal with the role of waste management and its significance to economic strategies and urban development during the late Roman Imperial Period and Late Antiquity. The findings contribute to highlighting top-down societal and economic pressures, rather than environmental degradation, as key factors involved in the ruralisation of the Negev agricultural heartland toward the close of Late Antiquity.

Earthquake damage as a catalyst to abandonment of a Middle Bronze Age settlement: Tel Kabri, Israel.

For years there has been much speculation surrounding the abandonment of the Middle Bronze Age IIB palace of Tel Kabri, ca. 1700 BCE. There are no weapons, hoards of money and jewelry, or visible evidence for fire, which rules out hostile attack or conquest. There are also no indications of drought or environmental degradation that might have forced the inhabitants to vacate the site, nor mass graveyards to indicate a pandemic. The current study uses micro-geoarchaeological methods to show that the demise of the palace was rapid, with walls and ceilings collapsing at once prior to abandonment. Macroscopic data (stratigraphic and structural) from five excavation seasons were reexamined, showing that at least nine Potential Earthquake Archaeological Effects (PEAEs) are found and associated with the last occupation phase of the site's palace. All lines of evidence point to the possibility that an earthquake damaged the palace, possibly to a point where it was no longer economically viable to repair. This conclusion is compounded by the discovery of a 1-3 m wide trench that cuts through the palace for 30 m, which may be the result of ground shaking or liquefaction caused by an earthquake. This study shows the importance of combining macro- and micro-archaeological methods for the identification of ancient earthquakes, together with the need to evaluate alternative scenarios of climatic, environmental, and economic collapse, as well as human-induced destruction before a seismic event scenario can be proposed.

Evidence of ritual breakage of a ground stone tool at the Late Natufian site of Hilazon Tachtit cave (12,000 years ago).

Destruction of valuables is a common behavior in human history. Ethnographic data show the polysemic, but fundamentally symbolic, nature of this act. Yet, research aimed at exploring symbolic destruction in prehistoric societies has underlined the difficulties in establishing unambiguous evidence for such behaviour. We present here the analysis of a basalt tool fragment which provides evidence for intentional breakage associated with ritual activity 12,000 years ago. The tool fragment was part of a unique assemblage of grave goods deposited in a burial pit of a woman suggested to have been a shaman (Hilazon Tachtit cave, Southern Levant). The reconstruction of the artefact's life history through morphological, 3D, use wear, residue and contextual analyses suggest that: 1) the fragment was initially part of a shallow bowl used for mixing ash or lime with water; 2) the bowl was subsequently intentionally broken through flaking along multiple axes; 3) The bowl was not used after its breakage but placed in a cache before the interment of the deceased, accompanied with other special items. The broken bowl fragment underlines the ritualistic nature of the act of breakage in the Natufian society. The research presented in this paper provides an important window into Natufian ritual behaviour during the critical period of transformation to agricultural communities. In addition, our results offer new insight into practices related to intentional destruction of valuables associated with death-related ceremonies at the end of the Palaeolithic.

Persistent Neanderthal occupation of the open-air site of 'Ein Qashish, Israel.

Over the last two decades, much of the recent efforts dedicated to the Levantine Middle Paleolithic has concentrated on the role of open-air sites in the settlement system in the region. Here focus on the site of 'Ein Qashish as a cases study. Located in present-day northern Israel, the area of this site is estimated to have been >1300 m2, of which ca. 670 were excavated. The site is located at the confluence of the Qishon stream with a small tributary running off the eastern flanks of the Mt. Carmel. At the area of this confluence, water channels and alluvial deposits created a dynamic depositional environment. Four Archaeological Units were identified in a 4.5-m thick stratigraphic sequence were dated by Optically Stimulated Luminescence (OSL) to between-71 and 54 ka, and probably shorter time span-~70-~60 ka. Here we present the diverse material culture remains from the site (lithics, including refitted sequences; modified limestone pieces; molluscs; faunal remains) against their changing paleogeographic backdrop. Skeletal evidence suggests that these remains were associated with Neanderthals. The large-scale repeated accumulation of late Middle Paleolithic remains in the same place on the landscape provides a unique opportunity to address questions of occupation duration and intensity in open-air sites. We find that each occupation was of ephemeral nature, yet presents a range of activities, suggesting that the locale has been used as a generalized residential site rather than specialized task-specific ones. This role of 'Ein Qashish did not change through time, suggesting that during the late Middle Paleolithic settlement system in this part of the southern Levant were stable.

Ancient trash mounds unravel urban collapse a century before the end of Byzantine hegemony in the southern Levant.

The historic event of the Late Antique Little Ice Age (LALIA) was recently identified in dozens of natural and geological climate proxies of the northern hemisphere. Although this climatic downturn was proposed as a major cause for pandemic and extensive societal upheavals in the sixth-seventh centuries CE, archaeological evidence for the magnitude of societal response to this event is sparse. This study uses ancient trash mounds as a type of proxy for identifying societal crisis in the urban domain, and employs multidisciplinary investigations to establish the terminal date of organized trash collection and high-level municipal functioning on a city-wide scale. Survey, excavation, sediment analysis, and geographic information system assessment of mound volume were conducted on a series of mounds surrounding the Byzantine urban settlement of Elusa in the Negev Desert. These reveal the massive collection and dumping of domestic and construction waste over time on the city edges. Carbon dating of charred seeds and charcoal fragments combined with ceramic analysis establish the end date of orchestrated trash removal near the mid-sixth century, coinciding closely with the beginning of the LALIA event and outbreak of the Justinian Plague in the year 541. This evidence for societal decline during the sixth century ties with other arguments for urban dysfunction across the Byzantine Levant at this time. We demonstrate the utility of trash mounds as sensitive proxies of social response and unravel the time-space dynamics of urban collapse, suggesting diminished resilience to rapid climate change in the frontier Negev region of the empire.

Ancient herders enriched and restructured African grasslands.

Grasslands are one of the world's most extensive terrestrial biomes and are central to the survival of herders, their livestock and diverse communities of large wild mammals1-3. In Africa, tropical soils are predominantly nutrient-limited4-6 but productive grassy patches in wooded grassland savannah ecosystems2,4 grow on fertile soils created by geologic and edaphic factors, megafauna, fire and termites4-6. Mobile pastoralists also create soil-fertility hotspots by penning their herds at night, which concentrates excrement-and thus nutrients-from grazing of the surrounding savannahs7-11. Historical anthropogenic hotspots produce high-quality forage, attract wildlife and increase spatial heterogeneity in African savannahs4,12-15. Archaeological research suggests this effect extends back at least 1,000 years16-19 but little is known about nutrient persistence at millennial scales. Here we use chemical, isotopic and sedimentary analyses to show high nutrient and 15N enrichment in on-site degraded dung deposits relative to off-site soils at five Pastoral Neolithic20 sites (radiocarbon dated to between 3,700 and 1,550 calibrated years before present (cal. BP)). This study demonstrates the longevity of nutrient hotspots and the long-term legacy of ancient herders, whose settlements enriched and diversified African savannah landscapes over three millennia.

The earliest modern humans outside Africa.

To date, the earliest modern human fossils found outside of Africa are dated to around 90,000 to 120,000 years ago at the Levantine sites of Skhul and Qafzeh. A maxilla and associated dentition recently discovered at Misliya Cave, Israel, was dated to 177,000 to 194,000 years ago, suggesting that members of the Homo sapiens clade left Africa earlier than previously thought. This finding changes our view on modern human dispersal and is consistent with recent genetic studies, which have posited the possibility of an earlier dispersal of Homo sapiens around 220,000 years ago. The Misliya maxilla is associated with full-fledged Levallois technology in the Levant, suggesting that the emergence of this technology is linked to the appearance of Homo sapiens in the region, as has been documented in Africa.

Evaluation of the Implantable Doppler Probe for Free Flap Monitoring in Lower Limb Reconstruction.

BACKGROUND: Timely reexploration and reanastomoses can salvage failing free flaps. The use of the implantable Doppler probe provides direct evidence of vascular impairment of the microvascular anastomoses and allows for postoperative NPWT. The aim of this retrospective study was to compare the Doppler probe to conventional monitoring techniques for free flap monitoring in lower limb reconstruction and to identify risk factors for perfusion disturbance and reexploration. METHODS: All patients receiving free muscle flap reconstruction for lower limb soft tissue defects at our department from 2000 to 2013 were included, and all adverse events, timely detection of perfusion problems, and outcome of revision surgery were assessed by chart analysis. RESULTS: For lower limb reconstruction, 110 free muscle transfers were performed of which 41 muscle flaps were conventionally monitored and 69 flaps were monitored using the implantable Doppler probe. In 18 cases, the free muscle flaps needed revision because of perfusion disturbances. The salvage rate was 80% with monitoring by the implantable Doppler probe compared with 62.5% using conventional monitoring methods resulting in success rates of 95.7 and 92.7%, respectively. CONCLUSION: The use of the implantable Cook-Swartz Doppler probe represents a safe monitoring method for lower limb reconstruction, which allows for the additional use of NPWT. Higher salvage and revision success rates can be attributed to an earlier detection of perfusion impairment. However, a larger patient cohort is necessary to verify superiority over conventional postoperative monitoring.

Formation of Biphasic Hydroxylapatite-Beta Magnesium Tricalcium Phosphate in Heat Treated Salmonid Vertebrae.

Ichthyoarchaeological evidence is uncommon at ancient hunter-gatherer sites from various regions and timeframes. This research contributes to the development of microarchaeological techniques useful for identifying fishing economies in situations where classifiable bones are unavailable. Specifically, traces of heat altered bone mineral in domestic hearths are expected to provide markers for discarded fish remains. We used a series of laboratory incineration experiments to characterize the mineralogy of burned salmonid vertebrae. Fourier transform infrared spectroscopy and x-ray diffraction distinguished the formation of beta magnesium tricalcium phosphate (ßMgTCP) at temperatures as low as 600 °C. Bones from a sample of game mammals and birds did not form this phase at temperatures below 1,000 °C. We propose that this neoformed mineral can serve as a proxy for hunter-gatherer salmonid fishing when typical ichthyoarchaeological evidence is absent. Using Fourier transform infrared spectroscopy, it will be possible to rapidly and inexpensively determine the presence of ßMgTCP in fragmentary burned bone remains associated with combustion features. The occurrence of ßMgTCP in archaeological hearth features will offer a new means of further evaluating the temporal, geographic, and cultural scope of salmonid harvesting. We also acknowledge the value of biphasic hydroxylapatite-ßMgTCP recovered from Atlantic salmon vertebrae as a bioceramic.

The first Neanderthal remains from an open-air Middle Palaeolithic site in the Levant.

The late Middle Palaeolithic (MP) settlement patterns in the Levant included the repeated use of caves and open landscape sites. The fossil record shows that two types of hominins occupied the region during this period-Neandertals and Homo sapiens. Until recently, diagnostic fossil remains were found only at cave sites. Because the two populations in this region left similar material cultural remains, it was impossible to attribute any open-air site to either species. In this study, we present newly discovered fossil remains from intact archaeological layers of the open-air site 'Ein Qashish, in northern Israel. The hominin remains represent three individuals: EQH1, a nondiagnostic skull fragment; EQH2, an upper right third molar (RM3); and EQH3, lower limb bones of a young Neandertal male. EQH2 and EQH3 constitute the first diagnostic anatomical remains of Neandertals at an open-air site in the Levant. The optically stimulated luminescence ages suggest that Neandertals repeatedly visited 'Ein Qashish between 70 and 60 ka. The discovery of Neandertals at open-air sites during the late MP reinforces the view that Neandertals were a resilient population in the Levant shortly before Upper Palaeolithic Homo sapiens populated the region.

Understanding fossil phytolith preservation: the role of partial dissolution in paleoecology and archaeology.

Opaline phytoliths are important microfossils used for paleoecological and archaeological reconstructions that are primarily based on relative ratios of specific morphotypes. Recent studies have shown that phytolith assemblages are prone to post-depositional alteration involving partial dissolution, however, the manner in which partial dissolution affects morphotype composition is poorly understood. Here we show that morphotype assemblages from four different plant species subjected to controlled partial dissolution are significantly different from the original assemblages, indicating that the stability of various morphotypes differs, mainly depending on their surface area to bulk ratios. This underlying mechanism produces distorted morphotype compositions in partially dissolved phytolith assemblages, bearing vast implications for morphotype-based paleoecological and archaeological interpretation. Together with analyses of phytolith assemblages from a variety of archaeological sites, our results establish criteria by which well-preserved phytolith assemblages can be selected for accurate paleoecological and archaeological reconstructions.

Archaeological horizons and fluvial processes at the Lower Paleolithic open-air site of Revadim (Israel).

In this paper we present new data pertaining to the paleo-landscape characteristics at the Acheulian site of Revadim, on the southern coastal plain of Israel. Sedimentological, isotopic, granulometric and micromorphological studies showed that the archaeological remains accumulated in an active fluvial environment where channel action, overbank flooding and episodic inundation occurred. Measurements of total organic matter and its carbon isotopic composition indicate that the hominin activity at the site started at a period of relatively drier conditions, which coincided with erosion of the preceding soil sequence. This process led to the formation of a gently-undulating topography, as reconstructed by a GIS model. Later deposition documents relatively wetter conditions, as indicated by carbon isotopic composition. Formation processes identified at the site include fluvial processes, inundation episodes that resulted in anaerobic conditions and formation of oxide nodules, as well as small-scale bioturbation and later infiltration of carbonate-rich solutions that resulted in the formation of calcite nodules and crusts. The combination of micro-habitats created favorable conditions that repeatedly drew hominins to the area, as seen by a series of super-imposed archaeological horizons. This study shows that site-specific paleo-landscape reconstructions should play an important role in understanding regional variation among hominin occupations and in extrapolating long-term behavioral patterns during the Middle Pleistocene.

Excited-state dynamics of protochlorophyllide revealed by subpicosecond infrared spectroscopy.

To gain a better understanding of the light-induced reduction of protochlorophyllide (PChlide) to chlorophyllide as a key regulatory step in chlorophyll synthesis, we performed transient infrared absorption measurements on PChlide in d4-methanol. Excitation in the Q-band at 630 nm initiates dynamics characterized by three time constants: τ1 = 3.6 ± 0.2, τ2 = 38 ± 2, and τ3 = 215 ± 8 ps. As indicated by the C13'=O carbonyl stretching mode in the electronic ground state at 1686 cm⁻¹, showing partial ground-state recovery, and in the excited electronic state at 1625 cm⁻¹, showing excited-state decay, τ2 describes the formation of a state with a strong change in electronic structure, and τ3 represents the partial recovery of the PChlide electronic ground state. Furthermore, τ1 corresponds with vibrational energy relaxation. The observed kinetics strongly suggest a branched reaction scheme with a branching ratio of 0.5 for the path leading to the PChlide ground state on the 200 ps timescale and the path leading to a long-lived state (>>700 ps). The results clearly support a branched reaction scheme, as proposed previously, featuring the formation of an intramolecular charge transfer state with ∼25 ps, its decay into the PChlide ground state with 200 ps, and a parallel reaction path to the long-lived PChlide triplet state.

Primary photoinduced protein response in bacteriorhodopsin and sensory rhodopsin II.

Essential for the biological function of the light-driven proton pump, bacteriorhodopsin (BR), and the light sensor, sensory rhodopsin II (SRII), is the coupling of the activated retinal chromophore to the hosting protein moiety. In order to explore the dynamics of this process we have performed ultrafast transient mid-infrared spectroscopy on isotopically labeled BR and SRII samples. These include SRII in D(2)O buffer, BR in H(2)(18)O medium, SRII with (15)N-labeled protein, and BR with (13)C(14)(13)C(15)-labeled retinal chromophore. Via observed shifts of infrared difference bands after photoexcitation and their kinetics we provide evidence for nonchromophore bands in the amide I and the amide II region of BR and SRII. A band around 1550 cm(-1) is very likely due to an amide II vibration. In the amide I region, contributions of modes involving exchangeable protons and modes not involving exchangeable protons can be discerned. Observed bands in the amide I region of BR are not due to bending vibrations of protein-bound water molecules. The observed protein bands appear in the amide I region within the system response of ca. 0.3 ps and in the amide II region within 3 ps, and decay partially in both regions on a slower time scale of 9-18 ps. Similar observations have been presented earlier for BR5.12, containing a nonisomerizable chromophore (R. Gross et al. J. Phys. Chem. B 2009, 113, 7851-7860). Thus, the results suggest a common mechanism for ultrafast protein response in the artificial and the native system besides isomerization, which could be induced by initial chromophore polarization.

Ultrafast protein conformational alterations in bacteriorhodopsin and its locked analogue BR5.12.

Bacteriorhodopsin, reconstituted with a sterically "locked" retinal chromophore, BR5.12, has frequently been used to elucidate elementary photoinduced processes in the native pigment bacteriorhodopsin. In this work, the vibrational response of BR5.12 to photoexcitation is investigated by means of femtosecond time-resolved mid-infrared and UV-vis spectroscopy. The electronically excited state of BR5.12 decays with a time constant of 18 ps. Neither in the UV-vis nor in the mid-IR spectral region are indications found for chromophore photoproducts, besides the full recovery of the electronic ground state. However, vibrational bands are observed at around 1660 and 1550 cm(-1) in the protein amide I and amide II band regions, respectively. They are formed within a few picoseconds or even instantaneously. Thus, they appear faster than the S1 decay and persist for at least 130 ps, i.e., for much longer than the S1 lifetime. These findings strongly suggest that the observed bands must be assigned to protein vibrations and that they are not caused by a photoinduced temperature rise. Thus, for the first time, ultrafast protein vibrational changes are detected in BR5.12, that are not associated with isomerization. Possibly they can be related to the enhanced chemical reactivity of photoactivated BR5.12 reported in the literature. In wild-type bacteriorhodopsin, bands with very similar spectral and kinetic characteristics are observed, suggesting that they might originate from a similar mechanism which is not isomerization. A plausible mechanism is a polarization induced protein conformational change, as discussed in the literature.

Ultrafast infrared spectroscopy of riboflavin: dynamics, electronic structure, and vibrational mode analysis.

Femtosecond time-resolved infrared spectroscopy was used to study the vibrational response of riboflavin in DMSO to photoexcitation at 387 nm. Vibrational cooling in the excited electronic state is observed and characterized by a time constant of 4.0 +/- 0.1 ps. Its characteristic pattern of negative and positive IR difference signals allows the identification and determination of excited-state vibrational frequencies of riboflavin in the spectral region between 1100 and 1740 cm (-1). Density functional theory (B3LYP), Hartree-Fock (HF) and configuration interaction singles (CIS) methods were employed to calculate the vibrational spectra of the electronic ground state and the first singlet excited pipi* state as well as respective electronic energies, structural parameters, electronic dipole moments and intrinsic force constants. The harmonic frequencies of the S 1 excited state calculated by the CIS method are in satisfactory agreement with the observed band positions. There is a clear correspondence between computed ground- and excited-state vibrations. Major changes upon photoexcitation include the loss of the double bond between the C4a and N5 atoms, reflected in a downshift of related vibrations in the spectral region from 1450 to 1720 cm (-1). Furthermore, the vibrational analysis reveals intra- and intermolecular hydrogen bonding of the riboflavin chromophore.

Sub-picosecond time resolved infrared spectroscopy of high-spin state formation in Fe(ii) spin crossover complexes.

The photoinduced low-spin (S = 0) to high-spin (S = 2) transition of the iron(ii) spin-crossover systems [Fe(btpa)](PF(6))(2) and [Fe(b(bdpa))](PF(6))(2) in solution have been studied for the first time by means of ultrafast transient infrared spectroscopy at room temperature. Negative and positive infrared difference bands between 1000 and 1065 cm(-1) that appear within the instrumental system response time of 350 fs after excitation at 387 nm display the formation of the vibrationally unrelaxed and hot high-spin (5)T(2) state. Vibrational relaxation is observed and characterized by the time constants 9.4 +/- 0.7 ps for [Fe(btpa)](PF(6))(2)/acetone and 12.7 +/- 0.7 ps for both [Fe(btpa)](PF(6))(2)/acetonitrile and [Fe(b(bdpa)](PF(6))(2)/acetonitrile. Vibrational analysis has been performed via DFT calculations of the low-spin and high-spin state normal modes of both compounds as well as their respective infrared absorption cross sections. The simulated infrared difference spectra are dominated by an increase of the absorption cross section upon high-spin state formation in accordance with the experimental infrared spectra.

Subpicosecond midinfrared spectroscopy of the Pfr reaction of phytochrome Agp1 from Agrobacterium tumefaciens.

Phytochromes are light-sensing pigments found in plants and bacteria. For the first time, the P(fr) photoreaction of a phytochrome has been subject to ultrafast infrared vibrational spectroscopy. Three time constants of 0.3 ps, 1.3 ps, and 4.0 ps were derived from the kinetics of structurally specific marker bands of the biliverdin chromophore of Agp1-BV from Agrobacterium tumefaciens after excitation at 765 nm. VIS-pump-VIS-probe experiments yield time constants of 0.44 ps and 3.3 ps for the underlying electronic-state dynamics. A reaction scheme is proposed including two kinetic steps on the S(1) excited-state surface and the cooling of a vibrationally hot P(fr) ground state. It is concluded that the upper limit of the E-Z isomerization of the C(15) = C(16) methine bridge is given by the intermediate time constant of 1.3 ps. The reaction scheme is reminiscent of that of the corresponding P(r) reaction of Agp1-BV as published earlier.