Unveiling Mechanistic Insights and Photocatalytic Advancements in Intramolecular Photo-(3 + 2)-Cycloaddition: A Comparative Assessment of Two Paradigmatic Single-Electron-Transfer Models.

The synthesis of 1-aminonorbornane (1-aminoNB), a potential aniline bioisostere, through photochemistry or photoredox catalysis signifies a remarkable breakthrough with implications in organic chemistry, pharmaceutical chemistry, and sustainable chemistry. However, an understanding of the underlying mechanisms involved in these reactions remains limited and ambiguous. Herein, we employ high-precision CASPT2//CASSCF calculations to elucidate the intricate mechanisms regulating the intramolecular photo-(3 + 2)-cycloaddition reactions for the synthesis of 1-aminoNB in the presence or absence of the Ir-complex-based photocatalyst. Our investigations delve into radical cascades, stereoselectivity, particularly single-electron-transfer (SET) events, etc. Furthermore, we innovatively introduce and compare two SET models integrating Marcus electron-transfer theory and transition-state theory. These models combined with kinetic data contribute to recognizing the critical control factors in diverse photocatalysis, thereby guiding the design and manipulation of photoredox catalysis as well as the improvement and modification of photocatalysts.

Unraveling the potential of segment scan mass spectral acquisition for chemical isotope labeling LC-MS-based metabolome analysis: Performance assessment across different types of biological samples.

BACKGROUND: Chemical isotope labeling (CIL) LC-MS is a powerful tool for metabolome analysis with high metabolomic coverage and quantification accuracy. In CIL LC-MS, the overall metabolite detection efficiency using Orbitrap MS can be further improved by employing a segment scan method where the full m/z range is divided into multiple segments for spectral acquisition with a significant increase in the in-spectrum dynamic range. Considering the metabolic complexity in different types of biological samples (e.g., feces, urine, serum/plasma, cell/tissue extracts, saliva, etc.), we report the development and evaluation of the segment scan method for metabolome analysis of different sample types. RESULTS: It was found that sample complexity significantly influenced the performance of the segment scan method. In metabolically complex samples such as feces and urine, the method yielded a substantial increase (up to 94 %) in detected peak pairs or metabolites, compared to conventional full scan. Conversely, less complex samples like saliva exhibited more modest gains (approximately 25 %). Based on the observations, a 120-m/z segment scan method was determined as a routine approach for CIL LC-Orbitrap-MS-based metabolomics with good compatibility with different types of biological samples. For this method, a further investigation on relative quantification accuracy was done. The peak area ratios of 12C-/13-labeled metabolites were slightly reduced with 72%-84 % of peak pairs falling within the ±25 % range of the anticipated peak ratio of 1.0 among different samples, as opposed to 81%-90 % in the full scan, which was attributed to the inclusion of more low-abundance peak pairs within the narrow MS segments. However, the overall peak ratio measurement precision was not significantly affected by the segment scan. SIGNIFICANCE AND NOVELTY: The segment scan method was found to be useful for CIL LC-Orbitrap-MS-based metabolome analysis of different types of samples with significant improvement in metabolite detectability (25-94 % increase), compared to the conventional full scan method.

Comparative Transcriptomic Assessment of Chemosensory Genes in Adult and Larval Olfactory Organs of Cnaphalocrocis medinalis.

The rice leaf folder, Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), is a notorious pest of rice in Asia. The larvae and adults of C. medinalis utilize specialized chemosensory systems to adapt to different environmental odors and physiological behaviors. However, the differences in chemosensory genes between the olfactory organs of these two different developmental stages remain unclear. Here, we conducted a transcriptome analysis of larvae heads, male antennae, and female antennae in C. medinalis and identified 131 putative chemosensory genes, including 32 OBPs (8 novel OBPs), 23 CSPs (2 novel CSPs), 55 ORs (17 novel ORs), 19 IRs (5 novel IRs) and 2 SNMPs. Comparisons between larvae and adults of C. medinalis by transcriptome and RT-qPCR analysis revealed that the number and expression of chemosensory genes in larval heads were less than that of adult antennae. Only 17 chemosensory genes (7 OBPs and 10 CSPs) were specifically or preferentially expressed in the larval heads, while a total of 101 chemosensory genes (21 OBPs, 9 CSPs, 51 ORs, 18 IRs, and 2 SNMPs) were specifically or preferentially expressed in adult antennae. Our study found differences in chemosensory gene expression between larvae and adults, suggesting their specialized functions at different developmental stages of C. medinalis. These results provide a theoretical basis for screening chemosensory genes as potential molecular targets and developing novel management strategies to control C. medinalis.

Exploring the impact mechanism of low-carbon multivariate coupling system in Chinese typical cities based on machine learning.

Low-carbon city construction is one of the key issues that must be addressed for China to achieve high-quality economic development and meet the Sustainable Development Goals. This study creates a comprehensive evaluation index system of low-carbon city multivariate system based on carbon emission data from 30 typical Chinese cities from 2006 to 2017 and evaluates and analyzes the trend of city low-carbon levels using the CRITIC-TOPSIS technique and MK method. Meanwhile, the influence mechanism of the multi-coupled system is investigated using the coupling coordination degree model and random forest algorithm.The results show that there are 8 cities with a significant increasing trend of low-carbon level, 19 cities with no significant monotonic change trend, and 3 cities with a decreasing trend of low-carbon level. By analyzing the coupling coordination degree, we found that the coupling coordination degree between low-carbon level and economic development in most cities tends to increase year by year, from the initial antagonistic effect to a good coordination development trend, which confirms the "inverted U-shaped" relationship between economy and carbon emission. In addition, industrial pollutant emissions, foreign direct investment, and economic output are the core drivers of low-carbon levels in cities.

Epidemiology and the economic burden of traumatic fractures in China: A population-based study.

Objectives: National data on the admission rate, distribution, in-hospital mortality, and economic burden of traumatic fractures in China is unclear. We aimed to conduct a cross-sectional population-based study to determine such above data at the national level in China. Methods: A national administrative database was used to review all traumatic fracture hospitalizations in China during 2020, from which a total of 2,025,169 inpatients with traumatic fractures was retrieved. Admission rates and in-hospital mortality rates stratified by age, sex, and region were calculated. The causes of traumatic fracture and economic burden were described. Results: The admission rate of traumatic fractures of all China population in 2020 was 1.437‰. The admission rate increased with age and varied with genders and causes of injuries. Falls are the leading cause of traumatic fracture hospitalization, followed by road traffic injuries. The most common diagnoses were femoral neck fractures, with a number of 138,377. The in-hospital mortality was 1.209‰. Road traffic injuries led to the highest in-hospital mortality. The median length of stay was 10 days, with the median hospitalization cost of ¥20,900 (about $3,056). Conclusion: Traumatic fractures are concerning conditions with a high admission rate and in-hospital mortality in China, which are mainly caused by falls and road traffic injuries. The government should implement more public health policies to enhance the health of the elderly and improve transportation safety to prevent traumatic fractures.

Spatio-temporal effect of provincial technological innovation on environmental pollution in China.

The relationship between technological innovation (TL) and environmental pollution (EP) and its action mechanisms are complex and controversial aspects of discussion. Using the spatial autocorrelation analysis, standard deviation ellipse analysis, kernel density function, spatial econometric model, this study analyzed the spatial distribution, evolution characteristics, and influencing factors of the EP and TL from 2000 to 2020 in China. Results found there was a significant spatial autocorrelation between the EP and TL in 2000-2020. The standard deviation ellipse of EP was broadly distributed in the "southwest-northeast" direction, indicating that EP presented a trend of concentration in the direction of "southwest-northeast." The moving trajectory of the center of gravity for the EP in 2000-2020 was essentially moved from the northeast to southwest. Overall, the national level of TL exhibited a "north-south change, high in the east, and low in the west" trend. Regional differences were gradually expanding, and the polarization was evident. Regardless of using least squares method (OLS) or quantile regression (QR) models, TL, human capital (HC), and industrial structure (IS) all had an inhibitory effect on the EP at the effective significance level. Total population (TP), foreign direct investment (FDI), and local fiscal expenditure (LFE) were positively related to the EP.

[Needs, Dilemmas, and Policy Suggestions Related to Patients With Mental Health Long-Term Care].

In Taiwan, The increase in life expectancy in Taiwan has increased the incidents of age-related problems among patients with mental illness. Therefore, the needs related to long-term care in mental health are significantly important. These needs include: (1) reducing stigmatization; (2) reducing the physical and economic burden of caregivers; (3) constructing a comprehensive, long-term care service system; and (4) developing assessment tools suitable to the long-term care of patients with mental illness. Moreover, six dilemmas in meeting long-term care needs were identified. These dilemmas include: (1) lack of a model of continuous care and of a platform for integrating hospital and community resources; (2) poor / inadequate service quality provided by certain community rehabilitation institutions; (3) the needs of patient/family centered care; (4) the persistence of stigma and misunderstanding; (5) the heavy burdens borne by family members providing long-term care; and (6) the disconnect between subsequent needs and the disability assessment system. Policy suggestions provided in this article include: (1) establish an inclusive platform for mental health long-term care information and resource integration; (2) construct long-term care centers for patients with mental health conditions; (3) train adequate manpower to provide long-term care services to these patients; and (4) promote community inclusiveness for these patients. In order to enter the era of long-term mental health care, government policy should target long-term care programs to meet the needs of patients with mental health conditions. These programs should include seamlessly integrating services into the long-term mental health care system and the care resources of community mental health, developing suitable assessment tools, establishing a multidisciplinary team of long-term care professionals to provide mental health care.

Development and Verification of an Economical Method of Custom Target Library Construction.

Although technological advances have greatly reduced the cost of DNA sequencing, sample preparation time and reagent costs remain the limiting factors for many studies. Based on low-cost targeted amplification, we developed an economical method for custom target library construction based on DNA nanoball (DNB) technology and two-step polymerase chain reaction (PCR). Here, we refer to this method as the two-step PCR, which was compared to traditional multiplex PCR methods in three aspects, data quality, efficiency, and specificity to humans. The results confirmed that two-step PCR reduces to finishing 128 sequencing libraries in only 2 h 24 min 59 s of the total PCR time and at a data utilization rate of 0.44 at a cost of approximately $1.70 per sample for targeted sequencing via the two-step PCR. The replacement of traditional multiplex PCR methods with this strategy makes the sample preparation process before sequencing relatively more cost-effective and further reduces the cost of next-generation sequencing (NGS). This method may also be free from the interference of other species and the limitations of sample type and DNA content. These findings reveal possibilities for broad applications of this approach in forensic research.

Estimating radiation exposure during paediatric cardiac catheterisation: a potential for radiation reduction with air gap technique.

INTRODUCTION: The air gap technique (AGT) is an approach to radiation dose optimisation during fluoroscopy where an "air gap" is used in place of an anti-scatter grid to reduce scatter irradiation. The AGT is effective in adults but remains largely untested in children. Effects are expected to vary depending on patient size and the amount of scatter irradiation produced. METHODS: Fluoroscopy and cineangiography were performed using a Phillips Allura Fluoroscope on tissue simulation anthropomorphic phantoms representing a neonate, 5-year-old, and teenager. Monte Carlo simulations were then used to estimate effective radiation dose first using a standard recommended imaging approach and then repeated using the AGT. Objective image quality assessments were performed using an image quality phantom. RESULTS: Effective radiation doses for the neonate and 5-year-old phantom increased consistently (2-92%) when the AGT was used compared to the standard recommended imaging approaches in which the anti-scatter grid is removed at baseline. In the teenage phantom, the AGT reduced effective doses by 5-59%, with greater dose reductions for imaging across the greater thoracic dimension of lateral projection. The AGT increased geometric magnification but with no detectable change in image blur or contrast differentiation. CONCLUSIONS: The AGT is an effective approach for dose reduction in larger patients, particularly for lateral imaging. Compared to the current dose optimisation guidelines, the technique may be harmful in smaller children where scatter irradiation is minimal.

Phylodynamic Characterization of an Ocular-Tropism Coxsackievirus A24 Variant.

Recent phylodynamic studies have focused on using tree topology patterns to elucidate interactions among the epidemiological, evolutionary, and demographic characteristics of infectious agents. However, because studies of viral phylodynamics tend to focus on epidemic outbreaks, tree topology signatures of tissue-tropism pathogens might not be clearly identified. Therefore, this study used a novel Bayesian evolutionary approach to analyze the A24 variant of coxsackievirus (CV-A24v), an ocular-tropism agent of acute hemorrhagic conjunctivitis. Analyses of the 915-nucleotide VP1 and 690-nt 3Dpol regions of 21 strains isolated in Taiwan and worldwide during 1985-2010 revealed a clear chronological trend in both the VP1 and 3Dpol phylogenetic trees: the emergence of a single dominant cluster in each outbreak. The VP1 sequences included three genotypes: GI (prototype), GIII (isolated 1985-1999), and GIV (isolated after 2000); no VP1 sequences from GII strains have been deposited in GenBank. Another five genotypes identified in the 3Dpol region had support values >0.9. Geographic and demographic transitions among CV-A24v clusters were clearly identified by Bayes algorithm. The transmission route was mapped from India to China and then to Taiwan, and each prevalent viral population declined before new clusters emerged. Notably, the VP1 and 3Dpol genes had high nucleotide sequence similarities (94.1% and 95.2%, respectively). The lack of co-circulating lineages and narrow tissue tropism affected the CV-A24v gene pool.

The value of routine biopsy during percutaneous kyphoplasty for vertebral compression fractures.

OBJECTIVE: Percutaneous kyphoplasty (PKP) is now widely performed to treat VCF, which is usually caused by osteoporosis. Previous researches have reported unsuspected malignancies found by biopsy. However, the safety and cost-effective profiles of routine biopsy during PKP are unclear. The purpose of this study was to evaluate the feasibility of routine biopsy during PKP in treatment of VCF. METHODS: Ninety-three patients (September 2007-November 2010) undergoing PKP without biopsy were reviewed as the control group. One hundred and three consecutive patients (November 2010-September 2013) undergoing PKP with biopsy of every operated vertebral level were prospectively enrolled as the biopsy group. The rate of unsuspected lesions was reported, and the severe adverse events, surgical duration, cement leakage rate and pain control were compared between the two groups. RESULTS: No statistically significant differences were found between the two groups, regarding the severe adverse events, surgical duration, cement leakage rate and pain control. Four unsuspected lesions were found in the biopsy group, three of which were malignancies with a 2.9% (3/103) unsuspected malignancy rate. The economic analysis showed that routine biopsy was cost-effective in finding new malignancies comparing with a routine cancer screening campaign. CONCLUSIONS: Routine biopsy during PKP was safe and cost-effective in finding unsuspected malignancies. We advocate routine biopsy in every operated vertebral level during PKP for VCF patients.

Evaluation of patient effective dose of neurovascular imaging protocols for C-arm cone-beam CT.

OBJECTIVE: The purpose of this study was threefold: to estimate the organ doses and effective doses (EDs) for seven neurovascular imaging protocols, to study the effect of beam collimation on ED, and to derive protocol-specific dose-area product (DAP)-to-ED conversion factors. MATERIALS AND METHODS: A cone-beam CT system was used to measure the organ doses for seven neurovascular imaging protocols. Two datasets were obtained: seven protocols without beam collimation (FOV, entire head) and four with beam collimation (FOV, from the base to the top of the skull). Measurements were performed on an adult male anthropomorphic phantom with 20 metal oxide semiconductor field-effect transistor (MOSFET) detectors placed in selected organs. The DAP values were recorded from the console. The EDs of five protocols were also estimated using Monte Carlo simulations software. The ED values were computed by multiplying measured organ doses to corresponding International Commission on Radiological Protection tissue-weighting factors. RESULTS: Without collimation, the EDs ranged from 0.16 to 1.6 mSv, and the DAP-to-ED conversion factors ranged from 0.035 to 0.076 mSv/Gy·cm(2). For the four protocols investigated with beam collimation, the ED was reduced by a factor of approximately 2, and the DAP-to-ED conversion factors were reduced by approximately 30%. For the five protocols also estimated with the Monte Carlo method, the estimated EDs were in agreement (< 20% deviation) with those determined by the MOSFET method. CONCLUSION: We have estimated ED for standard adult neuroimaging protocols in a 3D rotational angiography system. Our results provide a simple means of ED estimation using DAP console readings.

Toward an organ based dose prescription method for the improved accuracy of murine dose in orthovoltage x-ray irradiators.

PURPOSE: Accurate dosimetry is essential when irradiating mice to ensure that functional and molecular endpoints are well understood for the radiation dose delivered. Conventional methods of prescribing dose in mice involve the use of a single dose rate measurement and assume a uniform average dose throughout all organs of the entire mouse. Here, the authors report the individual average organ dose values for the irradiation of a 12, 23, and 33 g mouse on a 320 kVp x-ray irradiator and calculate the resulting error from using conventional dose prescription methods. METHODS: Organ doses were simulated in the Geant4 application for tomographic emission toolkit using the MOBY mouse whole-body phantom. Dosimetry was performed for three beams utilizing filters A (1.65 mm Al), B (2.0 mm Al), and C (0.1 mm Cu + 2.5 mm Al), respectively. In addition, simulated x-ray spectra were validated with physical half-value layer measurements. RESULTS: Average doses in soft-tissue organs were found to vary by as much as 23%-32% depending on the filter. Compared to filters A and B, filter C provided the hardest beam and had the lowest variation in soft-tissue average organ doses across all mouse sizes, with a difference of 23% for the median mouse size of 23 g. CONCLUSIONS: This work suggests a new dose prescription method in small animal dosimetry: it presents a departure from the conventional approach of assigninga single dose value for irradiation of mice to a more comprehensive approach of characterizing individual organ doses to minimize the error and uncertainty. In human radiation therapy, clinical treatment planning establishes the target dose as well as the dose distribution, however, this has generally not been done in small animal research. These results suggest that organ dose errors will be minimized by calibrating the dose rates for all filters, and using different dose rates for different organs.

CO2 uptake performance and life cycle assessment of CaO-based sorbents prepared from waste oyster shells blended with PMMA nanosphere scaffolds.

In this paper, we demonstrate a means of simultaneously solving two serious environmental issues by reutilization of calcinated mixture of pulverized waste oyster shells blending with poly(methyl methacrylate) (PMMA) nanospheres to prepare CaO-based sorbents for CO2 capture. After 10 cycles of isothermal carbonation/calcination at 750°C, the greatest CO2 uptake (0.19 g CO2/g sorbent) was that for the sorbent featuring 70 wt% of PMMA, which was almost three times higher than that (0.07 g CO2/g sorbent) of untreated waste oyster shell. The greater CO2 uptake was likely a result of particle size reduction and afterwards surface basicity enhancement and an increase in the volume of mesopores and macropores. Following simplified life cycle assessment, whose all input values were collected from our experimental results, suggested that a significant CO2 emission reduction along with lesser human health and ecosystems impacts would be achieved immediately once waste is reutilized. Most importantly, the CO2 uptake efficiency must be greater than 20% or sorbents prepared from limestone mining would eventually produce a net positive CO2 emission.

Protein-protein docking with backbone flexibility.

Computational protein-protein docking methods currently can create models with atomic accuracy for protein complexes provided that the conformational changes upon association are restricted to the side chains. However, it remains very challenging to account for backbone conformational changes during docking, and most current methods inherently keep monomer backbones rigid for algorithmic simplicity and computational efficiency. Here we present a reformulation of the Rosetta docking method that incorporates explicit backbone flexibility in protein-protein docking. The new method is based on a "fold-tree" representation of the molecular system, which seamlessly integrates internal torsional degrees of freedom and rigid-body degrees of freedom. Problems with internal flexible regions ranging from one or more loops or hinge regions to all of one or both partners can be readily treated using appropriately constructed fold trees. The explicit treatment of backbone flexibility improves both sampling in the vicinity of the native docked conformation and the energetic discrimination between near-native and incorrect models.

RosettaDock in CAPRI rounds 6-12.

A challenge in protein-protein docking is to account for the conformational changes in the monomers that occur upon binding. The RosettaDock method, which incorporates sidechain flexibility but keeps the backbone fixed, was found in previous CAPRI rounds (4 and 5) to generate docking models with atomic accuracy, provided that conformational changes were mainly restricted to protein sidechains. In the recent rounds of CAPRI (6-12), large backbone conformational changes occur upon binding for several target complexes. To address these challenges, we explicitly introduced backbone flexibility in our modeling procedures by combining rigid-body docking with protein structure prediction techniques such as modeling variable loops and building homology models. Encouragingly, using this approach we were able to correctly predict a significant backbone conformational change of an interface loop for Target 20 (12 A rmsd between those in the unbound monomer and complex structures), but accounting for backbone flexibility in protein-protein docking is still very challenging because of the significantly larger conformational space, which must be surveyed. Motivated by these CAPRI challenges, we have made progress in reformulating RosettaDock using a "fold-tree" representation, which provides a general framework for treating a wide variety of flexible-backbone docking problems.

[Heavy metal content and ecological risk warning assessment of vegetable soils in Chongming Island, Shanghai City].

In order to determine the content of copper (Cu), lead (Pb), chromium (Cr), zinc (Zn) and cadmium (Cd) in vegetable field, soil samples were collected from three towns of Chongming Island, an important ecotypic island of Shanghai City. The average content of Cu, Zn, Pb, Cr and Cd in vegetable soil of the three towns is 29.2 mg x kg(-1), 91.2 mg x kg(-1), 26.5 mg x kg(-1), 79.4 mg x kg(-1) and 0.222 mg x kg(-1), respectively. Except for the content of Cd exceeded the first grade of national soil standard (GB 15618-1995), the contents of the other four heavy metals were less than the first grade of the standard, and the content of heavy metals in this fireld met the request of heavy metal level to produce green foods (NY/T 391-2000). The contents of Cu, Pb, Cr, Zn and Cd in the vegetable soils are 24.3%, 24.4%, 22.9%, 18.8% and 65.7% higher than the background value of Shanghai, respectively. The result of ecological risk warning assessment showed that three sampling sites were medium warning situation, ten were light warning situation, eight were warning situation and one was no warning, in all the 23 sampling sites. The total situation of Chongming Island was light warning, and the I(ER) = 1.562. The order of ecological risk was Baozhen town (I(ER) = 1.799) > Chengqiaozhen town (I(ER) = 1.636) > Chenjiazhen (I(ER) = 1.368). The three towns were all light warning situation.

Progress in protein-protein docking: atomic resolution predictions in the CAPRI experiment using RosettaDock with an improved treatment of side-chain flexibility.

RosettaDock uses real-space Monte Carlo minimization (MCM) on both rigid-body and side-chain degrees of freedom to identify the lowest free energy docked arrangement of 2 protein structures. An improved version of the method that uses gradient-based minimization for off-rotamer side-chain optimization and includes information from unbound structures was used to create predictions for Rounds 4 and 5 of CAPRI. First, large numbers of independent MCM trajectories were carried out and the lowest free energy docked configurations identified. Second, new trajectories were started from these lowest energy structures to thoroughly sample the surrounding conformation space, and the lowest energy configurations were submitted as predictions. For all cases in which there were no significant backbone conformational changes, a small number of very low-energy configurations were identified in the first, global search and subsequently found to be close to the center of the basin of attraction in the free energy landscape in the second, local search. Following the release of the experimental coordinates, it was found that the centers of these free energy minima were remarkably close to the native structures in not only the rigid-body orientation but also the detailed conformations of the side-chains. Out of 8 targets, the lowest energy models had interface root-mean-square deviations (RMSDs) less than 1.1 A from the correct structures for 6 targets, and interface RMSDs less than 0.4 A for 3 targets. The predictions were top submissions to CAPRI for Targets 11, 12, 14, 15, and 19. The close correspondence of the lowest free energy structures found in our searches to the experimental structures suggests that our free energy function is a reasonable representation of the physical chemistry, and that the real space search with full side-chain flexibility to some extent solves the protein-protein docking problem in the absence of significant backbone conformational changes. On the other hand, the approach fails when there are significant backbone conformational changes as the steric complementarity of the 2 proteins cannot be modeled without incorporating backbone flexibility, and this is the major goal of our current work.

Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations.

Protein-protein docking algorithms provide a means to elucidate structural details for presently unknown complexes. Here, we present and evaluate a new method to predict protein-protein complexes from the coordinates of the unbound monomer components. The method employs a low-resolution, rigid-body, Monte Carlo search followed by simultaneous optimization of backbone displacement and side-chain conformations using Monte Carlo minimization. Up to 10(5) independent simulations are carried out, and the resulting "decoys" are ranked using an energy function dominated by van der Waals interactions, an implicit solvation model, and an orientation-dependent hydrogen bonding potential. Top-ranking decoys are clustered to select the final predictions. Small-perturbation studies reveal the formation of binding funnels in 42 of 54 cases using coordinates derived from the bound complexes and in 32 of 54 cases using independently determined coordinates of one or both monomers. Experimental binding affinities correlate with the calculated score function and explain the predictive success or failure of many targets. Global searches using one or both unbound components predict at least 25% of the native residue-residue contacts in 28 of the 32 cases where binding funnels exist. The results suggest that the method may soon be useful for generating models of biologically important complexes from the structures of the isolated components, but they also highlight the challenges that must be met to achieve consistent and accurate prediction of protein-protein interactions.