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1 The low-energy nature of these vibrations makes it difficult to access them experimentally, which

2 cal, individual production and comprehension makes it difficult to accommodate the ubiquitous, intera

3 ver, the cumulatively low incidence rate has made it difficult to accrue patients to prospective rand

4 cids are also affected by temperature, which makes it difficult to accurately determine the nucleic a

5 challenge of accounting for extinct species, making it difficult to accurately determine the underlyi

6 bryogenesis; yet, tedious sample preparation makes it difficult to acquire large-scale imaging data t

7 and intrinsic biological behaviors of cells makes it difficult to adequately describe cells, tissues

8 Such large distances make it difficult to align genomes and use them for comp

9 a strong reduction of CD4(+) T cells, which makes it difficult to analyze a functional role of CD83

10 A limited amount of high-quality evidence made it difficult to answer all the questions asked rela

11 t changes in how tornadoes are reported have made it difficult to answer it convincingly.

12 that there are limitations to the model that make it difficult to apply for a wide range of crops--pa

13 lack of permanent structure in these states makes it difficult to apply to them standard methods of

14 ferent databases and have different formats, making it difficult to apply LD score regression to esti

15 of evolution ensuring mutual survival, which makes it difficult to appreciate the underlying dynamics

16 on, where the presence of viral quasispecies makes it difficult to ascertain the true nature of the o

17 pts nucleocapsid formation in the cytoplasm, making it difficult to ascertain if the Core PPAY motif

18 The diversity of mononuclear phagocytes has made it difficult to ascribe cellular functions to sub-p

19 d, significant variation between studies has made it difficult to assess regulation of any given gene

20 interference with both cellular targets, has made it difficult to assess the unique consequences of V

21 suffer from vague-verbiage predictions that make it difficult to assess accuracy and improve policy.

22 d biological differences among these studies make it difficult to assess the generality of these prop

23 s highly variable over time and space, which makes it difficult to assess the average agronomic and e

24 aphic range and a variety of habitat types), makes it difficult to assess the long-term effectiveness

25 is balance between excitation and inhibition makes it difficult to assess the strength, or gain, of r

26 pitalizations, missing outpatient events and making it difficult to assess guideline adherence in ear

27 arkers vary across conditions and organisms, making it difficult to assess properties of cumulative d

28 ment of ice, atmospheric and marine records, making it difficult to assess relationships between Anta

29 in Vision and Ophthalmology Annual Meeting, making it difficult to assess risk for bias and applicab

30 s with this method require zygote injection, making it difficult to assess the adult, tissue-specific

31 BD in combination with one dose of oral THC, making it difficult to assess the nature of this interac

32 of a given species has yet to be undertaken, making it difficult to assess the origins of variability

33 ers affected by peripheral T-cell expansion, making it difficult to assess the role of thymic failure

34 dure for different error-correction methods, making it difficult to assess their relative merits and

35 mbiguity among the sequences of many strains makes it difficult to assign reads at the lowest level o

36 ormation on dynamics and intermediate states makes it difficult to associate the structural with the

37 imputed ones) fall into non-coding regions, making it difficult to associate statistical significanc

38 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly

39 detect interactions can be confounded, which makes it difficult to be certain that observed statistic

40 lenges that confront the private sector have made it difficult to capitalize on new opportunities pre

41 the low sensitivity of these techniques can make it difficult to capture dynamic muscle activity due

42 The heart's continuous motion makes it difficult to capture high-resolution images of

43 ong processing time before the final readout makes it difficult to capture transient signaling events

44 ediates, the transient nature of such states makes it difficult to characterize their structures.

45 o resolve forces across individual proteins, making it difficult to clearly establish if the LINC com

46 The large angles make it difficult to collect all of the coupled emission

47 SA has led to confusion in the field and has made it difficult to compare results across methods.

48 these measures are analysed and interpreted make it difficult to compare results across trials, and

49 The confounding variables make it difficult to compare studies.

50 re indices lacks a standardized methodology, making it difficult to compare published results.

51 may vary for different synthesis techniques, making it difficult to compare the suitability of differ

52 n thin tissue sections or upon live imaging, making it difficult to comprehensively localize dividing

53 hallenges in sample preparation and analysis make it difficult to confidently assign these numbers, l

54 ck of persistent and homogenous observations makes it difficult to confidently describe its interannu

55 tutively active is a significant limitation, making it difficult to confine knockdown to a specific l

56 too complex to be measured by this approach, making it difficult to connect genotype and phenotype at

57 hole-animal metabolic rate measurements have made it difficult to consistently demonstrate such a cos

58 This structural complexity has made it difficult to construct a reliable reference sequ

59 rveillance and reporting standards in Europe make it difficult to contain carbapenemase-producing Ent

60 at is responsible for the high mobility also makes it difficult to control their motion and prevents

61 er, the dynamic molecular processes involved make it difficult to correlate clustering with functiona

62 ypes is currently mostly performed manually, making it difficult to correlate phenotypic data to geno

63 complexity of protein machines, however, has made it difficult to create assemblies with both defined

64 is simple four-letter (A-T and G-C) language makes it difficult to create complex structures without

65 methods exist for orthology detection, which makes it difficult to decide which one to choose for a p

66 wever, limited observations of root dynamics make it difficult to define and predict patterns of root

67 This makes it difficult to define the baseline CFRs needed to

68 Nevertheless, linkage disequilibrium makes it difficult to define, without functional studies

69 are located outside protein-coding regions, making it difficult to define mechanism.

70 s compared with those diagnosed in the 1970s makes it difficult to definitively determine the effect

71 erstood and its high similarity to C-Src has made it difficult to delineate its function.

72 an existing polarity before EF application, making it difficult to delineate EF-specific pathways.

73 to modulate enzymes that alter PIP2 levels, making it difficult to delineate time- or region-specifi

74 st agents are polar and membrane impermeant, making it difficult to deliver them in sufficient quanti

75 troduced in whole-genome amplification (WGA) make it difficult to derive accurate genomic information

76 metal ions of similar size and charge, which makes it difficult to design a binding motif that is sel

77 in a polyploid species have high similarity, making it difficult to design genome-specific primers fo

78 ty to biopsy the affected tissue, the brain, making it difficult to design short and effective proof

79 combination with other more toxic therapies, making it difficult to design studies that allow appropr

80 in the overall enthalpy of the protein, thus making it difficult to detect experimentally.

81 line fluctuation exists between individuals, making it difficult to detect low level parasitemia.

82 his comes at the cost of positive-mean noise making it difficult to detect weak connections, which ar

83 nonical structure; however, limited sampling made it difficult to determine whether disordered sequen

84 The complexity of Cdk1 regulation has made it difficult to determine whether these different r

85 Earth's most rapidly uplifting mountains has made it difficult to determine whether weathering rates

86 n-cilia-related actions of some cilia genes, make it difficult to determine the basis of these polari

87 teeth that are rootless and homodont, which makes it difficult to determine dental homologies.

88 Reduction in mortality makes it difficult to determine the effect on hospitaliz

89 nts are "pan-HDAC" inhibitors, and their use makes it difficult to determine the roles of specific HD

90 or the use of genetically modified systems, making it difficult to determine the cell cycle stage of

91 ctual concentration of FA in these products, making it difficult to determine the intake of this vita

92 year to year in the absence of vaccination, making it difficult to determine what changes can be att

93 ivity and constricts cerebral blood vessels, making it difficult to determine whether cocaine-induced

94 equire multiple cognitive-control processes, making it difficult to determine which specific cognitiv

95 ingle-species and single-life stage studies, making it difficult to determine which taxa will be evol

96 intermediate transmission events, which has made it difficult to develop statistical tests to either

97 Such complexity makes it difficult to develop testable molecular hypothe

98 s a complex and heterogeneous mood disorder, making it difficult to develop a generalized, pharmacolo

99 evealing a high degree of interconnectivity, making it difficult to develop a simple, circuit-like un

100 s (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic

101 indirect transmission often remain untraced, making it difficult to develop control strategies.

102 n create extensive somatic genome diversity, making it difficult to develop versatile and scalable va

103 enecks in imaging and image processing often make it difficult to differentiate interesting biologica

104 s aggregated and aggregation-prone proteins, making it difficult to differentiate the mechanistic rol

105 er, the complex nature of p97 substrates has made it difficult to directly observe the fundamental ba

106 information on network formation in mammals, makes it difficult to directly investigate this hypothes

107 strict developmental requirement for SAP has made it difficult to discern its possible involvement in

108 outcome, although the later age at onset may make it difficult to discern if aortic stenosis or other

109 t in the different omics data sources, which makes it difficult to discern the coordinated signal of

110 ed strategies cannot be determined directly, making it difficult to discern the optimal strategy.

111 This robust association makes it difficult to discriminate normative age-related

112 up- or downregulated genes are often large, making it difficult to discriminate between dependent co

113 Often, programs used bundled interventions, making it difficult to discuss the efficiency and effect

114 environment evolves during cement formation, making it difficult to disentangle what factors are cruc

115 in interactions in this large structure have made it difficult to dissect the function of its compone

116 interconnectedness of cytoskeletal networks makes it difficult to dissect their individual effects o

117 the brain, the ubiquitous presence of NMDARs makes it difficult to dissociate direct effects from ind

118 However, technical challenges have made it difficult to distinguish whether altered respons

119 y trace for the event but, at the same time, make it difficult to distinguish it from plausible but n

120 sequenced, the presence of sequencing errors makes it difficult to distinguish between rare variants

121 ginated did not experience large expansions, making it difficult to distinguish among competing hypot

122 mutations is distributed across many genes, making it difficult to distinguish disease-relevant muta

123 ,5)P2 levels are slower than its metabolism, making it difficult to distinguish effects of PI(4,5)P2

124 rons are typically small and variable, often making it difficult to distinguish physiologically relev

125 of their requirement in canonical autophagy, making it difficult to distinguish the contributions of

126 f clearly determined neuropil boundaries has made it difficult to document precise locations of neuro

127 logies, feed compositions and patient groups makes it difficult to draw firm conclusions.

128 atic subsegmental PE (SSPE) are conflicting, making it difficult to draw conclusions about the approp

129 methods to assess SDB or cognitive domains, making it difficult to draw conclusions on this associat

130 based mostly on samples from western Europe, making it difficult to draw robust conclusions about the

131 e are highly variable from season to season, making it difficult to efficiently evaluate breeding pop

132 eristics of all of these viral proteins have made it difficult to elucidate their exact roles in viru

133 rocess of transcription affects supercoiling makes it difficult to elucidate the effects of H-DNA upo

134 ces that can lead to economic behaviors that make it difficult to escape poverty.

135 ions in obesity and microbiome research have made it difficult to establish causality in this complex

136 k of secondary pathology in these models has made it difficult to establish how amyloid deposition in

137 onflicting nature of the existing literature make it difficult to establish definitive predictive fac

138 species have fixed queen and worker castes, making it difficult to establish causality between the m

139 increasing number and interchangeable market make it difficult to estimate the real size of their con

140 nrecognised apparent dengue virus infections make it difficult to estimate the true extent of dengue

141 ble anti-Wolbachia and antifilarial effects, making it difficult to estimate therapeutic efficacy and

142 ons between MET and ERBB family members have made it difficult to evaluate the effects of MET on EGFR

143 This variation makes it difficult to evaluate PTBP1 binding to particul

144 This makes it difficult to evaluate the relationship between

145 uniformly succumbed to death within 6 days, making it difficult to evaluate host responses to infect

146 ing hydraulic conditions that produced them, making it difficult to evaluate the magnitude of paleo-f

147 c backgrounds influence cytokine production, making it difficult to evaluate which inflammatory profi

148 y conserved binding site with acetylcholine, making it difficult to evolve resistance yet maintain nA

149 r scaffolds often lowers the image contrast, making it difficult to examine cells and subcellular str

150 Data gaps make it difficult to explain trends, but legislative act

151 re destroyed during T1D disease progression, making it difficult to extensively study them in the pas

152 us presence of multiple different mechanisms makes it difficult to extract the information specific t

153 s of traditional risk factors with outcomes, making it difficult to extrapolate the results of trials

154 e low pH in the gastric juice of the stomach makes it difficult to fabricate stable and functional al

155 nt nature and heterogeneity of the oligomers make it difficult to follow their structure.

156 own about the invasion ecology of N. obtusa, making it difficult to forecast future expansion.

157 t stimulation, and spontaneous eye movements made it difficult to fully visualize the pupil.

158 ds, contains only two full cycles of the AMO making it difficult to fully characterize this oscillati

159 Such events are rare and stochastic, making it difficult to fully document how organisms resp

160 olutionary relatedness in plant communities, making it difficult to generalize responses of this majo

161 opology that comprise 50% of the structure, making it difficult to generate an accurate homology mod

162 This has made it difficult to identify consistent host factors th

163 plexity of genomic alterations in cancer has made it difficult to identify oncogenic drivers for the

164 These differences across many levels made it difficult to identify patterns in individual pro

165 This study used administrative data, which made it difficult to identify potential confounders and

166 However, redundancy among most miRNAs has made it difficult to identify their in vivo functions.

167 and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms

168 of K(+) than that of Li(+) and Na(+), which makes it difficult to identify a high-voltage and high-c

169 xt-dependent nature of protection mutualisms makes it difficult to identify and quantify the roles th

170 cause the complexity of the EE commonly used makes it difficult to identify causal aspects, we examin

171 ptiles, crucial for understanding evolution, makes it difficult to identify homologues of pallial div

172 icrosporidia, in North America or elsewhere, makes it difficult to identify the causes of such increa

173 This makes it difficult to identify the charge variants in a

174 ibe a base rate and co-occurrence issue that makes it difficult to identify the unique effects of chi

175 al isolates are negative for known adhesins, making it difficult to identify antigens for broad-cover

176 number of markers, which may be correlated, making it difficult to identify heterogeneity of risk fa

177 s the recognition of allergy-causing agents, making it difficult to identify the most appropriate all

178 vastly increases the scope of possible GEI, making it difficult to identify them with certainty.

179 ay become overwhelmed by the volume of data, making it difficult to incorporate newer information int

180 Such diversity has made it difficult to infer the impact of these modulator

181 y across neurons, even within a single area, making it difficult to infer their collective effect on

182 often lasts a few hundreds of milliseconds, making it difficult to infer underlying neural processes

183 ing of cell populations is not well defined, making it difficult to integrate the output of algorithm

184 Administration of interferons (IFNs) made it difficult to interpret biomarkers of immune acti

185 r, inherent biases in high-throughput assays make it difficult to interpret experiments in which more

186 within intronic or intergenic regions, which makes it difficult to interpret their functions.

187 onflict monitoring, and salience processing, making it difficult to interpret the dACC's specific psy

188 well as the overwhelming amounts of data can make it difficult to intuit patterns in the data or a me

189 with the influence of receptor polymorphisms makes it difficult to intuit the effect of beta-blockers

190 Their complexity makes it difficult to investigate the electron-phonon co

191 e multi-step oxygen reduction reaction (ORR) makes it difficult to investigate the oxygen dissociatio

192 This makes it difficult to isolate effects such as the role o

193 fferent sizes by competing mechanisms, which makes it difficult to isolate pathway-specific responses

194 form trypanosomes has not been investigated, making it difficult to judge the relative importance of

195 tific literature in the field of biomedicine makes it difficult to keep abreast of current knowledge,

196 ases is highly expensive and time-consuming, making it difficult to keep pace with the rapid growth o

197 ata and the complexity of traditional models make it difficult to leverage effectively.

198 ell type identification in awake animals has made it difficult to link interneuron activity with circ

199 -HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circui

200 ardization, and involve manual intervention, making it difficult to maintain data provenance and asse

201 is controlled by a diverse array of factors, making it difficult to make predictions about future lev

202 he intensity of the pain is highly variable, making it difficult to manage.

203 rain range boundaries are poorly understood, making it difficult to mechanistically project range shi

204 e that following such dietary guidance would make it difficult to meet recommended intakes for a numb

205 mplexity of mercury (Hg) biogeochemistry has made it difficult to model surface water concentrations

206 streamflow data or unimpaired flow scenarios makes it difficult to model TOC.

207 hed by sorting often have reduced viability, making it difficult to monitor the fate of transferred c

208 ental studies, but its slow folding rate has made it difficult to observe and characterize the foldin

209 However, the opaqueness of soil makes it difficult to observe how environmental factors

210 gh mosquito bites, and these common features make it difficult to obtain an accurate diagnosis by sym

211 1), whether there were general barriers that make it difficult to obtain an eye examination (P < 0.01

212 s (miRNAs) in small RNA sequencing libraries make it difficult to obtain efficient measurements of mo

213 d rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atr

214 inhomogeneity and low signal-to-noise ratio, making it difficult to obtain consistent activation patt

215 xtures suffer from intrinsic trade-offs that make it difficult to optimize both growth and transport

216 susceptibility to relevant human viruses and make it difficult to perform detailed molecular manipula

217 d with a rapid linkage disequilibrium decay, makes it difficult to perform genome-wide association (G

218 y, few chambers exist in the world, and this makes it difficult to perform large, multicenter clinica

219 z detection have limited dynamic range, thus making it difficult to perform some basic experiments th

220 tween surgical delivery and health outcomes, making it difficult to pinpoint a goal for surgical scal

221 mical and isotopic composition of the gases, making it difficult to pinpoint their origin.

222 The affected loci are often large, making it difficult to pinpoint which genes are driving

223 eform in a jerky way, with sudden slips that make it difficult to precisely control the deformation.

224 rting whole-grain intake have varied widely, making it difficult to precisely explore the relation of

225 This misunderstood property has made it difficult to predict the maximal tolerable dose

226 These countervailing effects make it difficult to predict population dynamics followi

227 elationships underlying malaria transmission make it difficult to predict the impact of interventions

228 Taken together, these variables make it difficult to predict the response of cell popula

229 respond to decadal changes in fire frequency makes it difficult to predict the effects of altered fir

230 ngue virus infection remain undefined, which makes it difficult to predict the efficacy of new vaccin

231 hological disparity of lophotrochozoan phyla makes it difficult to predict the morphology of the last

232 and/or electrophysiological characteristics makes it difficult to predict their physiological roles

233 and/or electrophysiological characteristics makes it difficult to predict their physiological roles

234 se effects varies among studies and systems, making it difficult to predict a priory how changes in p

235 t from coral to algal dominance are unknown, making it difficult to predict and plan for differing re

236 M photodegradation remain poorly understood, making it difficult to predict how inputs of thawing per

237 affected individuals can vary considerably, making it difficult to predict outcomes and determine th

238 n that a complex network of pathways exists, making it difficult to predict the effect of selected mi

239 standing of these costs remains fragmentary, making it difficult to predict the success of HGT events

240 ithelial tumors harbor numerous alterations, making it difficult to predict which genes are required

241 ut how these individuals progress over time, making it difficult to provide prognostic estimates.

242 emporal and spatial variability of processes make it difficult to quantify determinants of local-scal

243 is known about their spatial distributions, making it difficult to quantify their ecological signifi

244 This approach makes it difficult to rapidly change temperatures and en

245 s where infections are probably most common, making it difficult to reach conclusions on how populati

246 The lack of magnetism in PuCoGa5 has made it difficult to reconcile with most other heavy-fer

247 generalize fear to nonfearful fear stimuli, making it difficult to regulate anxiety.

248 The likelihood of multiple reaction pathways made it difficult to relate all differences in clearance

249 rge numbers of inputs onto a given V1 neuron make it difficult to relate them to the neuron's functio

250 cesses such as gliosis and fibrosis also can make it difficult to replenish and regenerate neurons.

251 statistical power of enrichment methods and make it difficult to replicate enrichment results across

252 complexity of the body's response to disease makes it difficult to represent this response with only

253 diversification is widespread in eukaryotes, making it difficult to resolve phylogenetic relationship

254 e sources and atmospheric circulation modes, making it difficult to resolve the drivers behind millen

255 between the hormones that regulate branching make it difficult to rule out other mechanisms of N acti

256 nal all-atom simulations of membrane systems makes it difficult to sample large rearrangements of lip

257 This makes it difficult to select treatment for patients with

258 its inherent heterogeneity and recalcitrance make it difficult to selectively valorize.

259 frontal cortex to the nucleus accumbens core makes it difficult to selectively enhance neuronal activ

260 o represent completely different structures, making it difficult to separate the potential impact of

261 patients analyzed in the previous study had made it difficult to separately analyze right-handed and

262 ype and subtype for efficient amplification, making it difficult to sequence samples with a rare or u

263 xity of these more realistic, spatial models makes it difficult to simulate realistically large and c

264 ERT and the lack of adequate antibodies have made it difficult to study telomerase-related processes

265 -A/C, lamin-B1, and lamin-B2, in mammals has made it difficult to study the assembly and function of

266 ches using the full-length, contiguous ORF2p make it difficult to study the involvement of these unan

267 biopolymers in solution; however, diffusion makes it difficult to study the same molecule for extend

268 ion that requires ATP and E1 and E2 enzymes, makes it difficult to study these ligases for basic rese

269 y prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ.

270 s substantial conformational rearrangements, making it difficult to study in its native state.

271 eurobehavioral defects or neurodegeneration, making it difficult to study the etiology of AOA2.

272 atients with hydroxychloroquine retinopathy, making it difficult to surmise the clinical course of pa

273 e (MDR), whose various underlying mechanisms make it difficult to target.

274 ially intermingled with wake-active neurons, making it difficult to target the sleep neurons specific

275 bind to multiple autophagy organelle types, making it difficult to tease apart the subcellular mecha

276 n transcriptional differences can be subtle, making it difficult to tease out real differentially exp

277 ese cells is arduous, and the rarity of CSCs makes it difficult to test potential drug candidates in

278 cannot be measured directly, and this often makes it difficult to test theories of perceptual decisi

279 cellularly differentiated ontogenetic stage, making it difficult to test their various phylogenetic i

280 tion seen in other primary sensory cortices, making it difficult to test this view.

281 understanding of C cycle processes well but makes it difficult to track model behaviors.

282 development include host range specificity, making it difficult to translate from animal models to h

283 Its resistance to certain antifungal agents makes it difficult to treat, especially for patients und

284 ammatory responses remain poorly understood, making it difficult to treat this deleterious condition.

285 the retina and superior colliculus (SC) have made it difficult to uncover their precise mechanisms of

286 of the MCM2-7 complex in DNA replication has made it difficult to uncover these.

287 criptions of events, symptoms, and responses made it difficult to understand teens' experiences of as

288 e heterogeneities present in fractures which make it difficult to understand and predict the transpor

289 pha-beta isoform combinations; these results make it difficult to understand the physiological requir

290 structures for most RNAs are unknown, which makes it difficult to understand how RNA structure gover

291 in axons where degeneration begins, and this makes it difficult to understand the disease process.

292 bles, especially the NP-electrode interface, making it difficult to understand and predict how struct

293 ever, NS5A has no known enzymatic functions, making it difficult to understand daclatasvir's mode of

294 tudy the incremental benefit of ASP and RDT, making it difficult to understand the true benefits of e

295 ociated with superconductivity, however, has made it difficult to unravel the role of quantum fluctua

296 This makes it difficult to update abundance estimates after r

297 ites and overlapping substrate specificities make it difficult to use inhibitors or activity-based pr

298 The high error rates make it difficult to use this data alone, particularly w

299 ntribute to their circulating concentrations makes it difficult to use them in isolation as a biomark

300 of data generated by flow cytometry usually makes it difficult to visualize.

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