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   1  with one another and with experimental data difficult.                                              
     2 tion of protein structural ensembles remains difficult.                                              
     3 ting privacy in family-based studies is more difficult.                                              
     4 etermining its behavioral impact have proven difficult.                                              
     5 re, direct measurement of the LBHB energy is difficult.                                              
     6 stematic analysis of such data unnecessarily difficult.                                              
     7 rformance outcomes under untested conditions difficult.                                              
     8 ed clinical trials) blinding is usually more difficult.                                              
     9  its role in the pathogenesis of PD has been difficult.                                              
    10 oughput screening conditions is particularly difficult.                                              
    11  paCOS with patterns of interest have proven difficult.                                              
    12 the liver in live model organisms has proven difficult.                                              
    13 n humans and other great apes is notoriously difficult.                                              
    14 ss on the detailed study of satDNA structure difficult.                                              
    15 fying the relative success of the two can be difficult.                                              
    16 e manipulation within defined cells has been difficult.                                              
    17 ucidation of microbe-microbe interactions is difficult.                                              
    18 akes species-specific diagnosis of infection difficult.                                              
    19 otein-ligand complexes, which is notoriously difficult.                                              
    20  compounds with improved permeability can be difficult.                                              
    21  many uncertainties that make drug discovery difficult.                                              
    22 resolution makes accurate placement of atoms difficult.                                              
    23 e make detection of these rare variants very difficult.                                              
    24 on sequencing (NGS) data for analysis can be difficult.                                              
    25 ity level, making provision of interventions difficult.                                              
    26 ntation of multilocus model in GWAS is still difficult.                                              
    27 s to the functional Env entry unit extremely difficult.                                              
    28 n soft actuators with high strain density is difficult.                                              
    29 ons) and sleep-dependent plasticity has been difficult.                                              
    30 m these noisy high-throughput screens remain difficult.                                              
    31 f anthropogenic and natural sources remained difficult.                                              
  
  
  
  
  
    37 ir implementation into synthetic collagen is difficult and requires the replacement of the canonical 
  
  
    40 of endosomal dynamics in live cells remained difficult as these structures lie at or below the  250 n
    41 , isolation of an electrogenic strain proved difficult as transfer cultures failed to grow after mult
  
    43 cluster model, we labelled the clusters as: "Difficult asthma" (n = 132); "Early-onset mild atopic" (
    44 ignificantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant 
  
  
    47 on of species and ecosystems is increasingly difficult because anthropogenic impacts are pervasive an
    48 rburg virus (MARV) and Ravn virus (RAVV), is difficult because of substantial sequence variability.  
  
    50 ting benefit for individual patients remains difficult because of the heterogeneity in treatment resp
    51 terrelated at the single-cell level has been difficult because of the lack of techniques for multimod
  
  
    54 c) mutations for Mendelian disorders is more difficult, because of the abundance of benign heterozygo
  
  
  
  
  
  
    61 nsfer protein) inhibitors has had a long and difficult course with 3 compounds failing in phase III c
    62  increase sampling times and performance for difficult discriminations, arguing for temporal integrat
    63 entification using morphological criteria is difficult due the plasticity of these characteristics an
  
    65 he full-length structure of NEMO have proved difficult due to its apparent high conformational plasti
    66 g the TP domain for antiviral development is difficult due to the lack of homology to other proteins 
  
  
    69 d eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset a
  
  
    72 eous abortion (OR, 0.11; 95% CI, 0.02-0.53), difficult fetal transition (bradycardia [OR, 15.0; 95% C
    73 t forms of physical activity is particularly difficult for both the individual with type 1 diabetes a
  
  
    76 uates in intensity over time is particularly difficult for hearing-impaired listeners with a sensorin
    77 l biology and genetics of spermatogenesis is difficult for most species because it occurs within a co
    78 make analysis and prioritization of variants difficult for researchers with limited bioinformatics sk
  
  
  
    82 differences in experimental protocols, it is difficult, if not impossible, to make meaningful compari
    83 ification of direct regulatory mechanisms is difficult in animals or primary adipocytes due to these 
    84 of TiO2, a promising photocatalyst, has been difficult in both powder and thin-film forms due to the 
  
  
  
    88 ansport, deposition, and processing has been difficult, in contrast to the well-characterized genes i
    89 trogen loading, predicting emissions remains difficult, in part due to challenges in disentangling di
  
  
  
  
    94 on of eosinophilic esophagitis (EoE) remains difficult, particularly the assessment of the patient's 
  
    96 ies (bNAbs) for ebolaviruses is possible but difficult, potentially due to the rarity of bNAb clones 
  
  
  
   100 ll integrate to reach a desired outcome is a difficult problem that has been studied in great detail 
  
   102 ay be applicable to crystallization of other difficult protein targets, as well as to other crystalli
   103 in types of adulterants make their detection difficult, so that food authentication often poses a cha
   104 lly demanding and recognizing novel folds is difficult such that the majority of proteins have not be
  
   106 al Review also tries to exemplarily show how difficult synthetic and theoretical problems can eventua
   107 covalent bonding in-arguably-one of the most difficult systems to study, the Am-Cl interaction within
  
   109 tcomes included item difficulty (how easy or difficult the question was), item discrimination (how we
   110 arly in illness, making a clinical diagnosis difficult; therefore, laboratory testing is needed to co
   111 ccessful syntheses of eighty-eight otherwise difficult to access compounds, in up to 99 % yields, inc
  
   113 desirable for a variety of applications, but difficult to access with modern C-C bond-forming reactio
   114 ereoselective Baeyer-Villiger oxidations are difficult to achieve by classical chemical means, partic
   115 r the precise synaptic localization has been difficult to achieve due to the lack of adequate optical
  
  
  
   119  to the activity of these genes has remained difficult to address, due in part to unique challenges r
  
  
  
  
   124 abases and have different formats, making it difficult to apply LD score regression to estimate genet
  
   126  neocortex in human evolution, it has proven difficult to ascertain whether this extent of prefrontal
   127 e rate and drivers of population decline are difficult to assess accurately: species' surveys are typ
   128 e, atmospheric and marine records, making it difficult to assess relationships between Antarctic ice-
   129 variable over time and space, which makes it difficult to assess the average agronomic and economic i
  
   131 ed by peripheral T-cell expansion, making it difficult to assess the role of thymic failure in human 
   132 e recurrence rates when melanoma margins are difficult to assess, and recurrence rates are high with 
  
  
  
   136 inition transient species, and therefore are difficult to characterize using current experimental tec
  
  
  
  
  
  
   143 up next to the protein-solvent interface are difficult to compensate by interactions with the protein
   144 s in sample preparation and analysis make it difficult to confidently assign these numbers, limiting 
   145 versification shifts occur after WGDs, it is difficult to consider diversification and duplication to
  
  
   148 se nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple alle
   149 s a complex biological process that has been difficult to delineate in human colorectal cancer (CRC) 
   150 te enzymes that alter PIP2 levels, making it difficult to delineate time- or region-specific roles of
   151 molecules, and even nanoparticles, which are difficult to deploy in harsh reservoir conditions and wh
  
  
  
  
   156 ltiple comparisons, wherein true signals are difficult to detect on the background of all association
  
   158 vely between individuals, but it can be very difficult to determine the sources of this heterogeneity
   159 e-dimensional RNA structures are notoriously difficult to determine, and the link between secondary s
  
  
   162 pical breakfast, lunch, and dinner meals are difficult to distinguish because skipping meals and snac
  
  
  
  
   167 ctional activity of this efflux pump is more difficult to elucidate, especially at the single-cell le
  
  
   170 obesity and microbiome research have made it difficult to establish causality in this complex relatio
  
  
  
  
  
  
   177 s often lowers the image contrast, making it difficult to examine cells and subcellular structures.  
   178   These patterns of atypical development are difficult to explain with existing models that emphasize
   179 stant from the genes of origin, are far more difficult to find because millions of SNPs must currentl
  
  
  
   183  relatedness in plant communities, making it difficult to generalize responses of this major feature 
   184 at comprise  50% of the structure, making it difficult to generate an accurate homology model of the 
  
   186  Pocillopora (Lamarck, 1816) are notoriously difficult to identify morphologically with considerable 
   187 dia, in North America or elsewhere, makes it difficult to identify the causes of such increases.     
   188 ch as bound biexcitons, are possible but are difficult to identify unambiguously using linear optical
  
  
  
  
   193      However, current options are obtrusive, difficult to implement, and limited in their scope of ut
   194  the complexity of the data, it is sometimes difficult to infer information about classes that are no
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
   215 ition of two high-resolution views otherwise difficult to obtain due to steric constraints at high nu
   216 ptides and N-glycoproteins that are hitherto difficult to obtain for structural and functional studie
  
  
  
  
   221  materials and structures that are otherwise difficult to obtain, studies of the functions and proper
  
  
   224 omplex network of pathways exists, making it difficult to predict the effect of selected miRNAs on ag
   225 o decadal changes in fire frequency makes it difficult to predict the effects of altered fire regimes
  
   227 erably between systems and have proven to be difficult to predict, spurring the need for new tools to
  
   229 on-noble metal nanoparticles are notoriously difficult to prepare and stabilize with appropriate disp
   230 the other hand, alpha-sulfinyl chlorides are difficult to prepare with high levels of enantiopurity a
   231 most available pharmaceuticals, but they are difficult to produce recombinantly, like many other aggr
   232 tic structure of SN-38, it is typically very difficult to produce sub-100nm, SN-38-encapsulated nanop
  
   234 omolar to millimolar dissociation constants) difficult to quantify under biologically relevant condit
   235 linear increase in heat-related morbidity is difficult to quantify, hindering the attribution of dire
  
  
   238 anscription of any given gene makes it often difficult to quickly identify the biological relevant tr
  
  
   241 esize nanostructure assemblies that would be difficult to realize any other way and that could ultima
  
  
  
  
   246 lection are strongly interactive: it is more difficult to repeat a response in the context of a chang
  
   248  associated with biofilm formation are often difficult to resolve without extended courses of antibio
   249 s at the root of the animal tree have proven difficult to resolve, with the current debate focusing o
  
  
  
  
   254 eterminant of T cell efficacy, it has proven difficult to selectively induce T cells of high function
   255 ness and higher brain function, but has been difficult to selectively manipulate owing to cellular he
   256 ti-epileptic drugs on individual neurons are difficult to separate from their network-level actions. 
  
  
   259 d in the literature are highly disparate and difficult to structure, a new format of organizing, visu
  
  
  
  
  
   265 al role of these intracellular hydrogels are difficult to study, primarily due to technical challenge
  
  
  
  
  
  
   272 nt include host range specificity, making it difficult to translate from animal models to humans.    
  
  
  
  
  
   278 plant severe renal insufficiency remain more difficult to treat, due to mechanisms of drug metabolism
  
   280 complex reaction with membranes, it has been difficult to uncover the molecular process that underlie
   281 ere perceived as challenging to communicate, difficult to understand, unrealistic in terms of timelin
  
  
   284 n by the lack of functional annotations from difficult-to-characterize or rare cell populations.     
   285 cate that too long treatment times can cause difficult-to-handle modifications to the cellular redox 
   286    Pustular skin disorders are a category of difficult-to-treat and potentially life-threatening cond
   287 ed high morbidity in patients with severe or difficult-to-treat asthma despite standard-of-care treat
  
  
  
  
  
   293 re accurately than unfamiliar ones and under difficult viewing conditions when unfamiliar face recogn
  
   295 s classification into simple, prolonged, and difficult weaning ignored weaning failure and presuppose
   296 onal disorder of identical nanostructures is difficult, which in turn has limited experimental verifi
   297 itis is under-recognized, since diagnosis is difficult with concomitant central nervous system (CNS) 
  
   299 rning protein-ligand interactions has proven difficult, with determination of entropic contributions 
  
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